Fact-checked by Grok 2 weeks ago

Transfer RNA

Transfer RNA (tRNA), formerly known as soluble RNA (sRNA), is a class of short, non-coding RNA molecules that play a central role in protein synthesis by acting as adaptors between the nucleotide sequence of messenger RNA (mRNA) and the corresponding amino acid sequence of proteins.^[1] These molecules, typically comprising 70 to 90 nucleotides, are aminoacylated with specific amino acids at their 3' end and recognize complementary codons on mRNA via their anticodon loops, ensuring accurate translation of the genetic code during ribosome-mediated polypeptide assembly.^[2] tRNAs are ubiquitous across all domains of life and exhibit extensive post-transcriptional modifications that enhance their stability, folding, and decoding fidelity.^[3] The secondary structure of tRNA adopts a characteristic cloverleaf conformation, featuring four main arms: the acceptor stem for amino acid attachment, the D-arm involved in recognition by aminoacyl-tRNA synthetases, the anticodon arm for codon-anticodon pairing, and the T-arm that interacts with ribosomal proteins.^[4] In three dimensions, tRNAs fold into an L-shaped tertiary structure, with the anticodon at one end and the amino acid-binding site at the other, approximately 70 Å apart, which facilitates their precise positioning within the ribosome's A, P, and E sites during elongation.^[4] This conserved architecture, preserved through billions of years of evolution, underscores tRNA's ancient origins, with molecular fossils suggesting it predates the last universal common ancestor and may have contributed to the emergence of the genetic code.^[2] In the process of translation, tRNAs are first charged with their cognate amino acids by aminoacyl-tRNA synthetases (aaRS), enzymes that ensure specificity through recognition of both the tRNA's identity elements and the amino acid substrate.^[5] Once loaded, tRNAs enter the ribosome, where the anticodon base-pairs with mRNA codons in a wobble-tolerant manner, allowing a reduced set of tRNAs (often around 40-50 per organism) to decode all 61 sense codons.^[1] Beyond canonical translation, tRNAs and their fragments participate in regulatory roles, such as stress responses, apoptosis, and gene expression modulation, highlighting their multifaceted contributions to cellular physiology.^[3] The discovery of tRNA occurred in the mid-1950s through experiments led by Mahlon Hoagland, Paul Zamecnik, and Mary Louise Stephenson at the Massachusetts General Hospital, who identified a soluble RNA fraction in cell extracts that reversibly bound activated amino acids, serving as an intermediate in protein biosynthesis.^[6] This breakthrough, building on earlier work by Francis Crick's adaptor hypothesis, elucidated how genetic information flows from nucleic acids to proteins and laid the foundation for understanding the molecular basis of the genetic code.^[6] Subsequent structural studies in the 1960s and 1970s, including X-ray crystallography by researchers like Alexander Rich, confirmed tRNA's intricate folding and evolutionary conservation.^[7]

Fundamentals

Overview

Transfer RNA (tRNA) is an essential adaptor molecule that serves as the physical intermediary between the genetic code encoded in messenger RNA (mRNA) and the corresponding amino acid sequence of proteins during the process of protein synthesis, known as translation.^[8] By recognizing specific nucleotide triplets, or codons, in mRNA through base-pairing with its anticodon region, tRNA delivers the precise amino acid required to build the polypeptide chain at the ribosome.^[9] The genetic code consists of 61 sense codons that specify the 20 standard amino acids, with tRNA bridging the nucleic acid-based instructions of mRNA to the protein world by ensuring accurate codon-anticodon matching.^[10] This adaptor function, first conceptualized in Francis Crick's 1955 hypothesis, enables the faithful translation of genetic information into functional proteins across diverse biological systems. tRNA is universally present in all living organisms, including prokaryotes and eukaryotes, as well as in organelles such as mitochondria and chloroplasts, where it supports independent translation machinery derived from endosymbiotic origins.^[8] Eukaryotic cells typically contain 40–60 distinct tRNA species, sufficient to decode the 61 codons due to the wobble hypothesis allowing some tRNAs to recognize multiple synonymous codons.^[10] In terms of cellular abundance, tRNA constitutes approximately 10–15% of the total RNA in cells, reflecting its critical and high-demand role in sustaining ongoing protein synthesis.^[11]

Nomenclature

Transfer RNA, abbreviated as tRNA, is the standard short form for its full name, transfer ribonucleic acid.^[12] This nomenclature reflects its role in transferring amino acids during protein synthesis, distinguishing it from other RNA types like messenger RNA (mRNA) and ribosomal RNA (rRNA).^[13] Historically, tRNA was first identified in the 1950s as a low-molecular-weight RNA fraction that remained soluble during certain fractionation steps, leading to its initial designation as soluble RNA or sRNA. By the early 1960s, as its adaptor function in translation became clear, the term "transfer RNA" was adopted to emphasize its specific role in shuttling amino acids to the ribosome, replacing the more generic sRNA label.^[14]^[15] The primary naming convention for tRNAs is based on the specific amino acid they carry, using a superscript notation for the three-letter amino acid code, such as tRNA^{Ala} for alanine-specific tRNA or tRNA^{Phe} for phenylalanine-specific tRNA.^[16] This system, established in early compilations of tRNA sequences, allows precise identification of the tRNA's charging specificity by aminoacyl-tRNA synthetases.^[16] Alternative formats include hyphens, as in tRNA-Ala, particularly in genomic databases like GtRND, where names follow patterns such as tRNA-XXX-YYY (with XXX as the three-letter amino acid code and YYY indicating anticodon specifics).^[17] A key aspect of tRNA nomenclature is the distinction among isoacceptors, which are multiple tRNA variants that carry the same amino acid but possess different anticodons to decode synonymous codons.^[3] For instance, phenylalanine isoacceptor tRNAs include tRNA^{Phe} with anticodons GAA (reading UUC) and AAA (reading UUU), enabling recognition of both codons for phenylalanine while ensuring the same amino acid is incorporated.^[8] This diversity accommodates the degeneracy of the genetic code, with organisms typically having 2–6 isoacceptors per amino acid to optimize translation efficiency.^[3] Special nomenclature applies to methionine tRNAs to differentiate their roles in translation initiation and elongation. The initiator form, denoted tRNA^{iMet} or tRNAi^{Met}, is uniquely formylated in prokaryotes (as fMet-tRNA^{iMet}) or unmodified in eukaryotes to bind the ribosomal P-site at start codons.^[18] In contrast, the elongator tRNA^{Met} inserts internal methionines during chain extension and shares the same anticodon (CAU) but differs in structural features and modification patterns.^[19] This superscript "i" prefix highlights the initiator's specialized function, preventing its misuse in elongation.^[20]

Molecular Structure

Primary and Secondary Structure

Transfer RNA (tRNA) molecules possess a primary structure consisting of a linear chain of 70 to 90 ribonucleotides, with the 5' end typically beginning with a guanosine and the 3' end terminating in the invariant CCA sequence.^[21] This sequence length accommodates the functional elements required for amino acid attachment and codon recognition, while conserved positions across tRNAs ensure structural integrity. Among these, approximately 26 positions are invariant or semi-invariant, meaning they are identical or limited to specific bases (purines or pyrimidines) in nearly all tRNAs.^[22] Notable examples include the G18-G19 pair in the D-loop, which facilitates tertiary interactions, and the U55 position, universally modified to pseudouridine (ψ55), contributing to stability.^[23] The secondary structure of tRNA adopts a characteristic cloverleaf model, first elucidated from the sequencing of yeast alanine tRNA, featuring four main stems and four loops formed by intramolecular base pairing.^[24] The acceptor stem, formed by base pairing between the 5' and 3' termini (positions 1-7 with 66-72), culminates in the 3' CCA end, the site of covalent amino acid attachment during aminoacylation.^[25] The D-arm consists of a stem (positions 10-13 paired with 22-25) and a D-loop rich in dihydrouridine modifications; the anticodon arm includes a stem (positions 27-30 paired with 40-43) and the anticodon loop (positions 34-36) for mRNA interaction; and the TψC-arm comprises a stem (positions 49-54 paired with 58-63) and a TψC-loop containing the conserved TψCG sequence.^[26] Intercalated between the anticodon and TψC arms is the variable loop, which exhibits significant length variation from 3 to 21 nucleotides, distinguishing class I tRNAs, which have a short variable loop of 3–5 nucleotides, from class II tRNAs, which have a longer variable loop of 13–21 nucleotides that often forms a mini-helix with 4–5 base pairs.^[27] Base pairing in the stems primarily follows Watson-Crick rules (A-U, G-C), but non-canonical pairs such as G-U wobbles are prevalent, providing flexibility and stability to the structure; for instance, G-U pairs occur frequently in the D-stem and anticodon stem of various tRNAs.^[28] These wobble pairs, conserved across species, distort the helical geometry slightly but enhance overall folding fidelity.^[29]

Tertiary Structure

The tertiary structure of transfer RNA (tRNA) adopts a compact L-shaped conformation, resulting from the coaxial stacking and orthogonal orientation of its helical domains derived from the cloverleaf secondary structure.^[30] The acceptor stem paired with the T-arm forms the elongated arm of the L, extending approximately 70 Å, while the D-arm paired with the anticodon stem-loop constitutes the shorter arm, also around 70 Å in effective span, positioning the amino acid attachment site at the 3' end far from the anticodon triplet.^[31] This architecture was first elucidated through X-ray crystallography of yeast tRNA^Phe at 3 Å resolution in 1974, revealing the polynucleotide chain's continuous density and the overall fold's compactness.^[30] Stability of the L-shaped fold relies on tertiary interactions beyond the secondary helices, including conserved base pairs such as the 10–25 and 13–22 pairs that bridge the D- and T-loops to form the "elbow" region at the bend of the L.^[30] Additional hydrogen bonds and non-canonical base triples in the core further reinforce this elbow, while divalent magnesium ions (Mg^2+^) coordinate with phosphate groups to neutralize electrostatic repulsion and lock the structure, with contact ion pairs embedded in hydration shells contributing significantly to the folded equilibrium.^[32] These elements ensure the molecule's rigidity under physiological conditions, with Mg^2+^ concentrations above 1 mM promoting tight packing of the two domains.^[31] The tertiary fold exhibits conformational dynamics, with local fluctuations in loop regions allowing transitions between relatively open and closed states that modulate flexibility without disrupting the overall L-shape, as observed in molecular dynamics simulations and NMR studies.^[33] This core structure is highly conserved across prokaryotes and eukaryotes, particularly in the elbow region where D-T loop interactions maintain the perpendicular domain orientation, though eukaryotic tRNAs may incorporate additional modifications that subtly enhance stability in the variable loop adjacent to the elbow.^[34]

Anticodon and Recognition Sites

The anticodon loop of transfer RNA (tRNA) is a conserved structural feature consisting of a seven-nucleotide single-stranded region that protrudes from the anticodon stem in the L-shaped tertiary fold of the molecule. This loop positions the three critical anticodon nucleotides at positions 34, 35, and 36, which directly base-pair with the corresponding codon on messenger RNA (mRNA) during protein synthesis. The loop is flanked by a five-base-pair stem, and its sequence typically begins with a conserved uridine at position 33, which facilitates a sharp U-turn motif that reverses the direction of the phosphate backbone, enhancing flexibility and proper presentation of the anticodon for codon recognition. This U-turn is stabilized by hydrogen bonding between the uridine at position 33 and the nucleotide at position 35, allowing the anticodon bases to extend outward for efficient pairing. A key aspect of anticodon function is the wobble hypothesis, which explains how tRNAs can decode multiple synonymous codons despite the degeneracy of the genetic code. Proposed by Francis Crick, this hypothesis posits that the first base of the anticodon (position 34, known as the wobble position) permits non-standard base pairing with the third base of the mRNA codon, reducing the number of required tRNA species. For instance, uridine at position 34 can pair with either adenine or guanine in the codon, enabling a single tRNA to recognize two codons differing in the third position. This flexibility is crucial for efficient translation, as it accommodates the 61 sense codons with fewer than 61 tRNAs. Post-transcriptional modifications in the anticodon loop further refine recognition specificity and stability. Notably, inosine at position 34, formed by adenosine deamination, allows pairing with adenine, cytosine, or uracil in the codon, expanding the decoding capacity of certain tRNAs, such as those for arginine and isoleucine. These modifications, concentrated in the anticodon loop, prevent aberrant pairing and enhance fidelity by altering base geometry and hydrogen bonding patterns. Recognition sites beyond the anticodon are essential for tRNA aminoacylation, where specific identity elements in the tRNA sequence are recognized by aminoacyl-tRNA synthetases (aaRS). These elements include nucleotides in the anticodon and the acceptor stem, with the discriminator base at position 73 (often adenine, A73) playing a pivotal role in synthetase binding and specificity. For example, A73 serves as a major determinant for many aaRS, influencing the correct attachment of amino acids by modulating enzyme-tRNA interactions and preventing misacylation. Other identity elements, such as specific bases in the anticodon (e.g., positions 34-36 for certain synthetases), act in concert to ensure high-fidelity charging, with their locations varying by amino acid specificity across organisms.

Function in Translation

Aminoacylation

Aminoacylation is the essential process by which specific amino acids are covalently attached to their cognate transfer RNAs (tRNAs), enabling the accurate translation of genetic information into proteins. This reaction is catalyzed by aminoacyl-tRNA synthetases (aaRSs), a family of 20 enzymes in most organisms, each dedicated to one of the 20 standard amino acids. The process ensures that each tRNA carries the correct amino acid corresponding to its anticodon, a prerequisite for faithful protein synthesis.^[35] The aminoacylation reaction occurs in two discrete steps. In the first activation step, the aaRS binds the amino acid and ATP, forming an aminoacyl-adenylate (aminoacyl-AMP) intermediate and releasing inorganic pyrophosphate (PPi). This high-energy intermediate positions the carboxyl group of the amino acid for nucleophilic attack. In the second transfer step, the activated aminoacyl group is ligated to the 3'-terminal ribose of the tRNA, specifically the 2'- or 3'-hydroxyl group depending on the aaRS class, forming a stable ester bond and releasing adenosine monophosphate (AMP). The overall process consumes the energetic equivalent of two high-energy phosphate bonds from ATP, as the released PPi is subsequently hydrolyzed by pyrophosphatase to drive the reaction forward irreversibly.^[36]^[37] aaRS enzymes are structurally classified into two distinct classes based on their catalytic domains. Class I aaRSs, which include synthetases for amino acids such as cysteine, leucine, and isoleucine, feature a Rossmann nucleotide-binding fold and typically attach the aminoacyl group to the 2'-OH of the tRNA terminal adenosine. In contrast, Class II aaRSs, responsible for amino acids like alanine, histidine, and proline, possess an antiparallel β-sheet core and acylate the 3'-OH. This structural dichotomy reflects evolutionary divergence while maintaining functional specificity, with each class encompassing synthetases for roughly half of the 20 amino acids.^[38]^[39] To achieve high fidelity despite the chemical similarities among amino acids, aaRSs employ proofreading (editing) mechanisms that correct errors in amino acid selection. These include pre-transfer editing, where non-cognate aminoacyl-AMP intermediates are hydrolyzed before transfer, and post-transfer editing, which hydrolyzes incorrectly charged aminoacyl-tRNAs after ester bond formation. For instance, isoleucyl-tRNA synthetase hydrolyzes misactivated valyl-AMP or valyl-tRNA^Ile^ to prevent incorporation of valine at isoleucine codons, ensuring translation accuracy rates exceeding 99.9%. Such editing domains are integral to many aaRSs, particularly those charging physicochemically similar amino acids.^[40]^[41]

Ribosome Binding and Decoding

The ribosome features three primary tRNA-binding sites that facilitate the translation process: the A-site, where decoding occurs and the incoming aminoacyl-tRNA (aa-tRNA) initially binds; the P-site, which holds the peptidyl-tRNA for peptide bond formation; and the E-site, from which deacylated tRNA exits after translocation.02064-9) These sites ensure ordered progression of tRNAs during protein synthesis, with the A-site serving as the entry point for codon recognition.^[42] In the decoding process, the ternary complex of aa-tRNA, GTP, and elongation factor Tu (EF-Tu) in prokaryotes—or its eukaryotic homolog eEF1A—delivers the aa-tRNA to the A-site of the ribosome. Upon initial codon-anticodon pairing in the A-site, the ribosome undergoes an induced fit conformational change, stabilizing cognate interactions while rejecting near-cognate or non-cognate tRNAs.^[43] This recognition triggers GTP hydrolysis by EF-Tu or eEF1A, which accelerates the release of the factor and allows tRNA accommodation into the A-site for subsequent peptide bond formation.^[44] In eukaryotes, decoding involves additional structural rearrangements in the ribosome, distinct from prokaryotic mechanisms, enhancing fidelity through prolonged monitoring of the codon-anticodon duplex.^[43] Kinetic proofreading enhances decoding accuracy by introducing a GTP hydrolysis step that divides tRNA selection into initial selection and proofreading phases, allowing erroneous tRNAs to dissociate before irreversible accommodation.^[45] During proofreading, near-cognate aa-tRNAs are rejected at higher rates following EF-Tu dissociation, achieving error rates as low as 10^{-4} for mistranslation.^[46] This two-step mechanism amplifies discrimination beyond simple base-pairing thermodynamics.^[42] Wobble pairing, particularly at the third position of the codon, enables a single tRNA to recognize multiple synonymous codons, reducing the number of required tRNAs while maintaining code degeneracy.^[47] Post-transcriptional modifications at the tRNA wobble position (position 34) fine-tune this flexibility, influencing base-pairing geometry monitored by the ribosomal decoding center.^[47] For instance, inosine at the wobble site allows pairing with U, C, or A, exemplifying how structural adaptations promote efficient decoding without compromising specificity.^[47] Following initial recognition, the tRNA undergoes accommodation into the A-site, involving domain rearrangements where the tRNA body rotates and the CCA end aligns for peptidyl transfer, a process accelerated by GTP hydrolysis.^[44] Cryo-EM structures reveal that this step includes transient interactions stabilizing the codon-anticodon helix within the small subunit's decoding center.^[42]

Role in Elongation and Termination

During the elongation phase of translation, the ribosome facilitates peptide bond formation between the growing polypeptide chain attached to the tRNA in the P-site and the amino acid carried by the incoming aminoacyl-tRNA (aa-tRNA) positioned in the A-site. The peptidyl transferase center, an RNA-based ribozyme within the large ribosomal subunit, catalyzes this nucleophilic attack by positioning the α-amino group of the A-site aa-tRNA to attack the carbonyl carbon of the peptidyl-tRNA ester bond in the P-site, resulting in chain elongation without external energy input beyond GTP hydrolysis in prior steps.00185-2) Following peptide bond formation, the ribosome enters a hybrid state where the anticodons of both tRNAs remain paired with their mRNA codons, but the peptidyl-tRNA shifts to an A/P hybrid position and the deacylated tRNA to a P/E hybrid, priming translocation. In prokaryotes, elongation factor G (EF-G), bound to GTP, interacts with the ribosome to drive the unidirectional movement of the tRNAs and mRNA, relocating the new peptidyl-tRNA to the P-site, the deacylated tRNA to the E-site for subsequent exit, and advancing the mRNA by one codon to expose the next codon in the A-site.^[48]^[49] In eukaryotes, the homologous elongation factor 2 (eEF2) performs this GTP-dependent translocation, ensuring efficient cycling through multiple rounds of elongation to build the polypeptide.^[50] The deacylated tRNA is then ejected from the E-site, completing the cycle and maintaining high throughput, with ribosomes capable of adding up to 20 amino acids per second in prokaryotes.^[48] Translation elongation achieves high fidelity, with error rates approximately 1 in 10,000 codons incorporated, primarily due to kinetic proofreading during tRNA selection and translocation that discriminates against near-cognate tRNAs.^[51]^[52] Upon encountering a stop codon in the A-site, translation terminates as class I release factors—RF1 or RF2 in prokaryotes, which recognize UAA/UGA or UAA/UAG respectively, and eRF1 in eukaryotes, which decodes all three stop codons (UAA, UAG, UGA)—bind to the ribosomal A-site in a tRNA-mimetic manner.81331-8)80667-4) These factors induce a conformational change in the peptidyl transferase center, positioning a conserved GGQ motif to activate a water molecule for hydrolysis of the ester bond linking the completed polypeptide to the P-site tRNA, releasing the nascent chain.^[53] In prokaryotes, RF3 (GTPase) then promotes release factor dissociation, while in eukaryotes, eRF3 assists similarly; recycling factor ABCE1 or homologs subsequently disassemble the post-termination ribosome.^[54]00263-X) Specialized suppressor tRNAs, often arising from mutations in standard tRNA genes, can compete with release factors by base-pairing with stop codons via altered anticodons, inserting an amino acid and allowing readthrough of premature termination signals; for example, amber suppressor tRNAs (supE or supF in E. coli) recognize UAG and insert glutamine or tyrosine, respectively, enabling continued elongation.^[55]90438-5.pdf) Such suppressors occur naturally at low frequencies but are harnessed in genetic studies and synthetic biology to rescue nonsense mutations.^[56]

Genetics and Evolution

tRNA Genes and Genomic Organization

Transfer RNA (tRNA) genes are primarily encoded in the nuclear genome of eukaryotes, where they exist in multiple copies to support the high demand for tRNA molecules during protein synthesis. In the budding yeast Saccharomyces cerevisiae, there are 275 nuclear-encoded tRNA genes, which collectively decode all 61 sense codons through 42 distinct tRNA species. In humans, the nuclear genome harbors approximately 610 tRNA genes, though nearly half are pseudogenes that do not produce functional tRNAs. These pseudogenes represent non-functional duplicates arising from gene duplication events, and their presence contributes to the overall redundancy in the tRNA gene repertoire.^[3]^[57] tRNA genes feature a conserved structure adapted for transcription by RNA polymerase III (Pol III). They contain internal promoter elements known as the A-box (typically located 8-19 nucleotides downstream of the transcription start site) and the B-box (52-62 nucleotides downstream), which are recognized by the transcription factor TFIIIC to recruit Pol III and initiate synthesis. In eukaryotes, a subset of tRNA genes includes a single intron positioned at the anticodon loop (nucleotide 37/38), with the frequency varying by species; for instance, approximately 20% of yeast tRNA genes (59 out of 275) contain such introns, while in humans, only about 7% of the ~400 potentially active genes do. These introns are removed during tRNA maturation but play roles in splicing regulation.^[58]^[59]^[60] Organelle-specific tRNA genes exhibit reduced diversity due to deviations in the genetic code and import mechanisms. The human mitochondrial genome encodes 22 tRNA genes, sufficient to translate the 13 mitochondrially encoded proteins using a modified code that reassigns certain codons. Similarly, chloroplast genomes in plants typically encode 30-37 tRNA genes, but many additional tRNAs are imported from the nuclear-cytosolic pool to supplement translation of chloroplast-encoded proteins. These organellar tRNAs often lack certain nuclear-encoded modifications and show structural adaptations for their environments.^[61]^[62] The genomic organization of tRNA genes varies across species, featuring both dispersed and clustered arrangements. In yeast, the 275 tRNA genes are scattered across chromosomes but show spatial clustering near centromeres (58%) and nucleolar regions, facilitating coordinated transcription. In vertebrates, tRNA genes are often found in tandem arrays or large clusters; for example, humans have a prominent cluster of 157 tRNA genes at chromosome 6p22.2, with overall 17-36% of genes organized in such clusters, reflecting lineage-specific expansions. This organization influences chromatin structure and expression efficiency, with pseudogenes interspersed among functional loci.^[63]^[64]^[65]

Evolutionary Origins

The core structure of transfer RNA (tRNA) is highly conserved across all domains of life, suggesting its emergence predates the last universal common ancestor (LUCA). Analyses of tRNA sequences and structures indicate that the L-shaped tertiary fold and key functional elements, such as the acceptor stem and anticodon loop, were likely present in the common ancestor of bacteria, archaea, and eukaryotes. This conservation is evidenced by the near-universal retention of a 31-nucleotide minihelix precursor, which formed the basis for the modern tRNA's coaxial stacking of stems.^[66]^[67] In the RNA world hypothesis, tRNA is posited to have originated as a proto-ribozyme capable of ligating amino acids to RNA oligomers, facilitating the transition from RNA-based to protein synthesis. Early tRNA-like molecules may have functioned in aminoacylation without protein catalysts, using ribozyme activity to attach amino acids via ester bonds at the 3' CCA end. The "genomic tag" hypothesis further proposes that the upper half of tRNA (acceptor stem and T-arm) evolved first as a terminal tag on RNA genomes, marking 3' ends for replication by ribozymes like RNase P, with the anticodon domain added later to adapt for translation.^[68] tRNA evolution coevolved with the genetic code, expanding from an initial set of fewer than 20 amino acids to the modern 20 through stepwise incorporation of new codons and synthetases. The wobble hypothesis, allowing non-standard base pairing at the anticodon's third position, minimized the required number of tRNA species from 61 to around 32-40, enabling efficient decoding with fewer isoacceptors. This degeneracy likely arose to accommodate code expansion while maintaining translational fidelity.^[69]^[70] In eukaryotic organelles, tRNA evolution reflects endosymbiotic gene transfer from bacterial ancestors to the nucleus, with most mitochondrial and chloroplast tRNAs encoded in the organelle genome but some imported from the cytosol. Mitochondrial tRNAs exhibit deviations from the universal code, such as AUA decoding as methionine rather than isoleucine, enabled by formylation and specific modifications like 5-formylcytosine at the anticodon wobble position. These changes arose post-endosymbiosis to adapt to reduced gene sets and altered codon usage.^[71]^[72] Comparative genomics reveals domain-specific differences in tRNA repertoires: bacterial tRNAs are generally simpler with fewer isodecoders, while archaeal tRNAs show intermediate complexity, and eukaryotic tRNAs possess more extensive post-transcriptional modifications—averaging around 13 per molecule compared to about 8 in prokaryotes—to enhance stability and decoding accuracy in diverse environments.^[73]^[74]^[75]

tRNA-Derived Fragments

Transfer RNA-derived fragments (tRFs), also known as tRNA-derived small RNAs (tsRNAs), are small non-coding RNAs generated from mature or precursor tRNAs through specific cleavage processes. These fragments typically range from 14 to 40 nucleotides in length and include two main categories: tRNA halves (tiRNAs), which are approximately 30-40 nucleotides long and produced by cleaving mature tRNAs at the anticodon loop, and shorter tRFs derived from the 5', 3', or TψC loops and other regions. tiRNAs are further subclassified into 5'-tiRNAs and 3'-tiRNAs based on their cleavage site, while tRFs encompass types such as 5'-tRFs, 3'-tRFs (e.g., CCA-tailed or CCA-truncated), and i-tRFs from the D-loop or anticodon loop. Stress-induced examples include tiRNA-Ala, which accumulates under hypoxic conditions.^[76]^[77]^[78] Biogenesis of tsRNAs primarily occurs through endonucleolytic cleavage of tRNAs by ribonucleases such as angiogenin (ANG) or Dicer, often triggered by cellular stress, apoptosis, or viral infection. Under stress conditions like oxidative stress or nutrient deprivation, ANG cleaves tRNAs at the anticodon loop to produce tiRNAs, while Dicer-dependent processing generates certain tRFs, particularly those resembling microRNAs. In apoptotic cells, caspase-mediated activation of RNases contributes to tsRNA production, and post-transcriptional modifications on tRNAs, such as m¹A or pseudouridine, influence cleavage site specificity and fragment stability. Unlike mature tRNA processing, tsRNA generation bypasses standard RNase P and RNase Z pathways, instead relying on stress-responsive mechanisms.^[76]^[79]^[78]^[80] tsRNAs exert diverse regulatory functions beyond canonical tRNA roles, including gene silencing through association with Argonaute proteins in RNA-induced silencing complexes (RISC), where they target mRNAs for degradation or translational repression. Specific tRFs, such as tRF-1001, inhibit translation by binding to the 80S ribosome and blocking elongation, while tiRNAs suppress global protein synthesis during stress by sequestering translation initiation factors like eIF2α. Additionally, certain tsRNAs, including 5'-tiRNA-Glu, inhibit retrotransposon activity by binding to reverse transcriptase enzymes, thereby preventing genomic insertions. These functions highlight tsRNAs' roles in fine-tuning gene expression and cellular responses to environmental cues.^[76]^[81]^[78]^[77] In disease contexts, tsRNAs are frequently upregulated and serve as biomarkers or regulators. In cancer, tRF-1001 is elevated in prostate and colon tumors, promoting proliferation and metastasis by modulating apoptosis pathways, while tiRNAs contribute to tumor angiogenesis via angiogenin signaling. Neurodegenerative disorders, such as Alzheimer's disease, show altered tsRNA profiles, with specific tRFs influencing amyloid-beta aggregation and neuronal survival. tsRNAs also link to cardiovascular diseases by regulating endothelial cell apoptosis and inflammation.^[79]^[80]^[82]^[83] Post-2010 research has uncovered tsRNAs' involvement in viral defense and epigenetic regulation. During viral infections, tiRNAs inhibit viral replication by suppressing host translation and interfering with viral protein synthesis, as seen in responses to influenza or hepatitis viruses. Epigenetically, tsRNAs influence DNA methylation and histone modifications; for instance, 5'-tRFs guide Argonaute proteins to promoter regions, repressing oncogenes in immune cells. Studies from the 2020s emphasize tsRNAs' roles in innate immunity, where they modulate interferon responses and T-cell differentiation, positioning them as potential therapeutic targets.^[76]^[81]^[79]^[80]

Biogenesis and Modifications

Transcription and Processing

In eukaryotes, transfer RNA (tRNA) genes are transcribed by RNA polymerase III (Pol III), which recognizes internal promoter elements within the transcribed sequence. These promoters consist of two conserved boxes: the A-box, located at nucleotides 8–19, and the B-box, at nucleotides 52–62, relative to the mature tRNA structure.^[58] The transcription factor complex TFIIIC binds these A- and B-boxes to recruit TFIIIB and Pol III, initiating synthesis of a primary tRNA transcript known as pre-tRNA.^[84] This internal promoter architecture allows efficient transcription without reliance on upstream elements, distinguishing Pol III promoters from those of Pol II.^[85] In prokaryotes, tRNA transcription is carried out by a single multisubunit RNA polymerase, similar to that used for mRNA and rRNA synthesis. Many bacterial tRNA genes are organized into polycistronic operons, where multiple tRNA precursors are transcribed as a single long primary transcript from a single promoter, often upstream of the operon.^[86] For instance, in Escherichia coli, tRNA genes like those in the valV-valW and leuQ-leuP-leuV operons are co-transcribed into polycistronic precursors that require subsequent processing to yield individual mature tRNAs.^[87] This arrangement enables coordinated expression of tRNAs needed for translation.^[88] Maturation of pre-tRNAs begins with endonucleolytic processing to remove flanking sequences. The 5' leader sequence is cleaved by ribonuclease P (RNase P), a ribonucleoprotein complex that generates the mature 5' end in both prokaryotes and eukaryotes.^[89] In prokaryotes, RNase P acts on polycistronic transcripts to release individual pre-tRNAs, often in a 5'-to-3' directional manner.^[90] The 3' trailer is trimmed by endonuclease RNase Z (also known as ElaC or Trz), which cleaves downstream of the discriminator base to produce the pre-tRNA with a mature 3' end, excluding the CCA sequence.^[91] In eukaryotes, a subset of pre-tRNAs (about 10-20% in yeast) contain introns that must be removed by splicing; this is catalyzed by the tRNA splicing endonuclease (TSEN) complex, which recognizes structural features of the pre-tRNA and excises the intron, followed by ligation of the exons.^[92] If the 3' end lacks the conserved CCA triplet required for aminoacylation, it is added post-transcriptionally by a template-independent CCA-adding enzyme, also known as tRNA nucleotidyltransferase. This enzyme uses CTP and ATP as substrates to polymerize the CCA sequence at the 3' terminus, ensuring functionality even if the primary transcript terminates imprecisely.^[93] The process involves sequential addition without a nucleic acid template, guided by recognition of the tRNA's acceptor stem.^[94] Quality control mechanisms during processing prevent export of defective tRNAs. In eukaryotes, misfolded pre-tRNAs are retained in the nucleus through surveillance pathways, such as the nuclear tRNA quality control system involving the TRAMP complex and exosome, which degrade aberrant precursors to maintain translational fidelity.^[95] This retention ensures only properly processed tRNAs proceed to the cytoplasm for modification and function.^[96]

Post-Transcriptional Modifications

Transfer RNA (tRNA) undergoes extensive post-transcriptional modifications, with over 100 distinct types identified across organisms, primarily involving methylation, isomerization, and base addition to enhance structural integrity and functional precision.^[3] These modifications occur at specific positions, such as pseudouridine (Ψ) formation at U55 in the T-loop, catalyzed by pseudouridine synthases of the Pus family, including Pus4 in yeast and Pus1 in humans.^[97] Similarly, N1-methylguanosine (m¹G) at position 37 adjacent to the anticodon is introduced by tRNA methyltransferase Trm5 in eukaryotes, preventing translational frameshifting by stabilizing the codon-anticodon interaction.^[98] Other notable examples include wybutosine (yW), a hypermodified guanosine at G37 in phenylalanine tRNA, synthesized through a multi-enzyme pathway involving TYW1 and TYW2, which strengthens base pairing and decoding accuracy.^[99] Enzymes responsible for these modifications belong to conserved families, such as tRNA methyltransferases (Trm proteins) that use S-adenosylmethionine as a methyl donor for sites like m¹A at A58 or m⁵C at the wobble position 34, and pseudouridine synthases that isomerize uridine without external donors.^[3] In the anticodon loop, modifications like queuosine (Q) at position 34 in tRNAs for asparagine, aspartate, histidine, and tyrosine, where the queuine base is acquired from diet or microbiota in eukaryotes and incorporated by enzymes such as QTRT1 and QTRT2, influencing translation efficiency and tRNA stability.^[100] Eukaryotes exhibit greater modification diversity—with around 90-100 distinct types known across tRNAs, and individual tRNAs bearing typically 5-20 modifications—compared to bacteria, which have fewer, simpler alterations.^[3]^[101] These modifications collectively stabilize the tRNA's L-shaped secondary structure, reduce conformational flexibility, and optimize ribosome interactions, with defects leading to impaired codon recognition and increased error rates.^[102] For instance, wybutosine at 37 enhances stacking interactions to prevent +1 frameshifting during elongation.^[99] Emerging research in epitranscriptomics highlights dynamic roles of these modifications in disease; hypomodification of mitochondrial tRNAs, such as τm⁵s²U34 in tRNA-Lys, underlies syndromes like MELAS and MERRF by disrupting oxidative phosphorylation protein synthesis.^[103] Similarly, reduced queuosine levels correlate with neurodegeneration and cancer progression, underscoring therapeutic potential in targeting modifying enzymes.^[104]

Applications and Clinical Relevance

Engineered and Synthetic tRNAs

Suppressor tRNAs are engineered variants of natural tRNAs with anticodon mutations that enable them to recognize premature stop codons, thereby facilitating read-through during translation and inserting a specific amino acid at the site.^[105] In Escherichia coli, the amber suppressor Su⁺7, derived from tRNA^Trp, features a CUA anticodon that decodes the UAG stop codon as glutamine, allowing suppression of amber mutations with efficiencies up to 76%.^[106] These suppressors have been constructed synthetically using oligonucleotides to introduce precise anticodon changes, enabling their use in amino acid substitution studies for protein engineering.^[107] Orthogonal tRNA/aminoacyl-tRNA synthetase (aaRS) pairs represent a cornerstone of genetic code expansion, where the tRNA and its cognate aaRS are engineered to avoid cross-reactivity with host translation machinery, specifically charging the tRNA with an unnatural amino acid (UAA).^[108] Pioneered by Peter Schultz's group, this approach uses amber suppression with an orthogonal tRNA^CUA and a mutated aaRS to incorporate UAAs at UAG sites in response to an amber codon in the target mRNA.^[109] A notable example is the incorporation of p-azido-L-phenylalanine, which enables site-specific photocrosslinking and bioorthogonal chemistry for protein labeling and conjugation.^[110] Synthetic tRNAs are produced through in vitro transcription, typically using T7 RNA polymerase to generate unmodified RNA transcripts that can be chemically aminoacylated or used directly in reconstituted translation systems.^[111] Minimal synthetic tRNAs, shortened to as few as 49 nucleotides while retaining core structural elements like the acceptor stem and anticodon, have demonstrated functionality in aminoacylation and ribosomal decoding, highlighting the modularity of tRNA architecture for custom designs.^[112] These engineered and synthetic tRNAs enable protein engineering by allowing site-specific UAA incorporation, expanding the genetic code to include over 100 diverse UAAs with novel properties such as fluorescence, photocrosslinking, or metal chelation.^[113] In therapeutics, suppressor tRNAs have shown promise for treating nonsense mutations in diseases like cystic fibrosis, where optimized variants enable partial restoration of full-length CFTR protein (up to ~14% of wild-type function) by read-through of premature termination codons without significantly disrupting normal translation.^[114] Recent advances in the 2020s include CRISPR-based delivery of suppressor tRNA genes into mammalian cells, achieving efficient nonsense suppression in vivo for gene therapy applications, and integration into synthetic biology for creating orthogonal translation systems in non-natural environments.^[115]

Diseases and Therapeutic Implications

Mutations in genes encoding tRNA synthetases, such as RARS2, which charges mitochondrial tRNA^Arg with arginine, cause pontocerebellar hypoplasia type 6 (PCH6), a severe autosomal recessive disorder characterized by cerebellar and pontine hypoplasia, microcephaly, and early-onset epilepsy.^[116] These mutations impair mitochondrial translation, leading to defective oxidative phosphorylation and progressive neurodegeneration, as observed in multiple families with biallelic RARS2 variants.^[117] Similarly, variants in other mitochondrial tRNA synthetase genes, like DARS2, result in leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL), highlighting tRNA charging defects as a recurring mechanism in mitochondrial encephalomyopathies.^[118] Defects in tRNA editing by aminoacyl-tRNA synthetases contribute to protein misfolding and neurodegeneration; for instance, editing-deficient alanyl-tRNA synthetase (AARS) in mice leads to accumulation of mischarged tRNAs, triggering intracellular protein aggregates in neurons and behavioral deficits reminiscent of amyotrophic lateral sclerosis (ALS).^[119] In the context of infectious diseases, human tRNA^Lys3 serves as the primer for HIV-1 reverse transcriptase during viral genome replication, and disruptions in its annealing or modification can inhibit reverse transcription, offering a potential antiviral target.^[120] Hypomodification of tRNAs, such as reduced m^1A58 in tRNA^Leu(UUR), is linked to type 2 diabetes; polymorphisms in CDKAL1, which methylates this site, impair beta-cell function and insulin secretion in both human cohorts and mouse models.^[121] In cancer, tRNA-derived fragments (tRFs) act as oncogenic regulators by promoting cell proliferation and inhibiting apoptosis; for example, the 3'-tRF-Val derived from tRNA^Val is upregulated in gastric cancer tissues, correlating with advanced tumor stages and enhanced migration via interaction with oncogenes like HMGB1.^[122] Similarly, tRF-03357 from tRNA^Glu promotes proliferation and invasion in high-grade serous ovarian cancer by suppressing HMBOX1 expression, underscoring tRFs' role in tumor progression across multiple malignancies.^[123] Genetic variants influencing tRF biogenesis further contribute to cancer susceptibility, as shown in genome-wide association studies linking tRF expression to breast and lung cancers.^[124] Therapeutically, engineered suppressor tRNAs delivered via lipid nanoparticles (LNPs) carrying their encoding mRNA enable read-through at premature termination codons in diseases like cystic fibrosis, achieving suppression efficiencies up to ~70% in preclinical models with minimal off-target effects, and show potential for Duchenne muscular dystrophy.^[114] For antibiotic resistance, external guide sequence antisense oligonucleotides targeting bacterial mRNAs involved in tRNA charging pathways, such as aac(6')-Ib in aminoglycoside-resistant strains, induce RNase P cleavage and restore susceptibility in vitro.^[125] Emerging tRNA-based gene therapies, including chemically modified tRNAs to enhance translation of therapeutic proteins, show promise in treating genetic disorders by boosting suppressor activity in vivo.^[126] tRNA modifications serve as diagnostic biomarkers in oncology; for instance, altered queuosine (Q) levels at the wobble position of tRNA^Asn and tRNA^Tyr, catalyzed by TGT enzyme, correlate with leukemia progression, with Q-deficient tRNAs elevated in acute myeloid leukemia cells as potential indicators of poor prognosis.^[127] In neurodegeneration, recent 2025 studies (as of November 2025) reveal disease-specific tRNA fragment profiles, such as increased tRF expression in Alzheimer's disease models derived from iPSC neurons, suggesting tRNA-derived signatures for early detection.^[128] Loss-of-function mutations in tRNA modification enzymes like TRMT1 cause neurodevelopmental disorders with hypomodified tRNAs, further implicating modification defects in cognitive decline across dementias.^[129]

Historical Development

Discovery and Early Characterization

In the mid-1950s, researchers at the Massachusetts General Hospital, including Mahlon B. Hoagland, Paul C. Zamecnik, and Mary Louise Stephenson, were investigating protein synthesis using cell-free extracts from rat liver. They observed that activated amino acids, formed by attachment to adenosine monophosphate (AMP) via specific enzymes, were rapidly bound to a fraction of RNA that remained soluble in the supernatant after high-speed centrifugation. This RNA, initially called "soluble RNA" (sRNA) or "pH 5 enzyme RNA," served as a carrier for these aminoacyl groups, preventing their immediate incorporation into proteins and suggesting an intermediate role in translation. Their seminal 1957 paper in Biochimica et Biophysica Acta detailed how each of the 20 common amino acids could be specifically attached to this sRNA fraction, laying the groundwork for understanding amino acid activation and transfer. Early experiments further elucidated sRNA's function as an adaptor molecule. Using pulse-labeling techniques with radioactive amino acids, Hoagland and colleagues demonstrated that labeling occurred first on sRNA within seconds, followed by slower transfer to nascent polypeptide chains on ribosomes. This temporal pattern, reported in 1958 in the Journal of Biological Chemistry, confirmed sRNA's role in bridging amino acids to the ribosomal machinery, aligning with Francis Crick's 1955 adaptor hypothesis. By 1961, as biochemical and genetic studies clarified its transfer function during protein synthesis, multiple groups—including those led by Zamecnik and François Gros—renamed it "transfer RNA" (tRNA) to reflect this specific role.^[6]^[130] A major advance came in 1965 when Robert W. Holley and his team at Cornell University achieved the first complete isolation and sequencing of a pure tRNA species: alanine tRNA from baker's yeast. This feat required processing over 1,400 pounds of yeast to yield just 1 gram of purified material, using techniques like countercurrent distribution and chromatography. Published in the Journal of Biological Chemistry, the 77-nucleotide sequence revealed tRNA's cloverleaf secondary structure, with an anticodon loop for codon recognition and an acceptor stem for amino acid attachment, providing the first direct evidence of its molecular architecture. This work not only validated tRNA's adaptor function but also enabled early efforts to decipher the genetic code.^[131] The foundational contributions to tRNA discovery were recognized in 1968, when Holley shared the Nobel Prize in Physiology or Medicine with Har Gobind Khorana and Marshall W. Nirenberg. Their collective efforts—Holley's structural elucidation of tRNA, Khorana's chemical synthesis of oligonucleotides to probe codon assignments, and Nirenberg's cell-free translation systems—unraveled how genetic information is translated into proteins via tRNA. The Nobel citation highlighted tRNA's central role in interpreting the genetic code, marking a pivotal moment in molecular biology.^[132]

Key Milestones and Advances

In the 1970s, significant strides were made in elucidating the three-dimensional architecture of tRNA, building on the secondary structure proposed earlier. The cloverleaf model, initially suggested based on sequence analysis, was experimentally confirmed through X-ray crystallography, revealing the conserved secondary structural elements such as stems and loops.^[30] A landmark achievement came in 1974 with the determination of the first atomic-resolution structure of yeast phenylalanyl-tRNA (tRNA^{Phe}) at 3 Å resolution, which demonstrated the L-shaped tertiary fold where the acceptor stem and T-arm form one arm, and the D-arm and anticodon arm form the other, oriented at a right angle. This structure by Kim, Rich, and colleagues provided the foundational model for understanding tRNA's role in bridging mRNA and protein synthesis.^[30]^[133] The 1980s advanced insights into tRNA charging mechanisms and genetic manipulation. Structural studies illuminated the aminoacylation process, with the first crystallization of a tRNA-aminoacyl-tRNA synthetase (aaRS) complex achieved in 1980 using yeast aspartyl-tRNA synthetase and tRNA^{Asp}, enabling subsequent atomic models that revealed how aaRS enzymes recognize specific tRNA identity elements for accurate amino acid attachment.^[134] Pioneering work also introduced suppressor tRNAs for expanding the genetic code; in 1989, engineered amber suppressor tRNAs were used to incorporate an unnatural amino acid (para-fluorophenylalanine) into proteins in a cell-free synthesis system from E. coli, marking an early step toward site-specific noncanonical amino acid incorporation. Subsequent work in the early 1990s extended this to in vivo incorporation in eukaryotic cells, such as yeast, using chemically aminoacylated suppressor tRNAs.^[109]^[135] During the 1990s and 2000s, genomic sequencing projects unveiled the organization and diversity of tRNA genes across organisms. Analysis of complete genomes, such as the Saccharomyces cerevisiae genome in 1996, identified multicopy tRNA gene families—often 10–20 isoacceptors per amino acid—clustered in specific loci and revealing evolutionary conservation alongside species-specific variations in anticodon usage. Refinements to the wobble hypothesis emerged, with the 1991 modified-wobble hypothesis proposing that specific post-transcriptional modifications at the anticodon wobble position (e.g., queuosine or wybutosine) restrict or expand codon recognition, explaining observed deviations from Crick's original 1966 rules through structural constraints on base pairing.^[136] In the 2010s, high-throughput sequencing technologies revolutionized the study of tRNA modifications and derived fragments. Methods like DM-tRNA-seq, developed around 2015, enabled quantitative detection and mapping of over 100 tRNA modifications (e.g., m^1A and i^6A) at single-nucleotide resolution by using demethylases to facilitate reverse transcription, uncovering dynamic modification patterns linked to translation fidelity. Concurrently, the discovery of tRNA-derived fragments (tRFs) and stress-induced tiRNAs in 2009 highlighted their regulatory roles; these 18–40 nucleotide RNAs, generated by angiogenin cleavage under stress, inhibit translation initiation by binding to eukaryotic initiation factor 4A and modulate gene expression in cancer and neurodegeneration. Recent advances in the 2020s have leveraged cryo-electron microscopy (cryo-EM) and computational tools for deeper mechanistic insights and engineering. High-resolution cryo-EM structures (2.5–3.5 Å) of tRNA-ribosome complexes, such as those from 2020 onward, have captured transient states during translocation and accommodation, revealing how tRNA conformational dynamics and modifications influence peptidyl transfer and frameshifting.^[137] In synthetic biology, genetic code expansion progressed with orthogonal tRNA/aaRS pairs enabling incorporation of over 200 noncanonical amino acids.

References

[1]
Transfer RNA function and evolution - Taylor & Francis Online
Aug 11, 2018 · Transfer RNA (tRNA) has a long-established role in protein synthesis. The tRNA molecule serves as an adaptor [1] between the genetic ...
[2]
Origins and Early Evolution of the tRNA Molecule - PubMed Central
Dec 3, 2015 · Modern transfer RNAs (tRNAs) are composed of ~76 nucleotides and play an important role as “adaptor” molecules that mediate the translation ...
[3]
Modifications and functional genomics of human transfer RNA - Nature
Feb 20, 2018 · The primary function of tRNA as the adaptor of amino acids and the genetic code in protein synthesis is well known. tRNA modifications play ...Human Trna Gene Features · Human Trna Modifications · Functional Genomics
[4]
Transfer RNA Structure and Identity - NCBI - NIH
The structure of tRNA and its relationship with the biological necessity of specific tRNA aminoacylation reactions, in other words with identity, is reviewed.
[5]
Aminoacyl-tRNA synthetases: Structure, function, and drug discovery
Aminoacyl-tRNA synthetases (AARSs) are the enzymes that catalyze the aminoacylation reaction by covalently linking an amino acid to its cognate tRNA in the ...
[6]
The Discovery of tRNA by Paul C. Zamecnik
Oct 7, 2005 · From this they concluded that the RNA, later named transfer RNA or tRNA, functions as an intermediate carrier of amino acids in protein ...
[7]
Structure of transfer RNAs: similarity and variability - WIREs RNA
Sep 28, 2011 · Transfer RNAs (tRNAs) are ancient molecules whose origin goes back to the beginning of life on Earth.<|control11|><|separator|>
[8]
Transfer RNAs: diversity in form and function - PMC - PubMed Central
This review analyzes tRNA structure, biosynthesis and function, and includes topics that demonstrate their diversity and growing importance.
[9]
From RNA to Protein - Molecular Biology of the Cell - NCBI Bookshelf
The genetic code is translated by means of two adaptors that act one after another. The first adaptor is the aminoacyl-tRNA synthetase, which couples a ...tRNA Molecules Match Amino... · Specific Enzymes Couple...
[10]
Transfer RNA function and evolution - PMC - PubMed Central - NIH
Transfer RNA (tRNA) has a long-established role in protein synthesis. The tRNA molecule serves as an adaptor [1] between the genetic instructions written in ...
[11]
percent of tRNA in total RNA - Mammalian tissue culture cell
percent of tRNA in total RNA ; Value, 15 % ; Organism, Mammalian tissue culture cell ; Reference, Molecular Cell Biology. 4th edition. Lodish H, Berk A, Zipursky ...
[12]
Transfer RNA (tRNA) - National Human Genome Research Institute
Transfer RNA (abbreviated tRNA) is a small RNA molecule that plays a key role in protein synthesis.
[13]
Nucleic Acid Symbols - IUPAC nomenclature
N-1.3.1. The two main types of nucleic acids are designated by their customary abbreviations, RNA (ribonucleic acid or ribonucleate) and DNA (deoxyribonucleic ...
[14]
CSHL | History | Mahlon Hoagland on 1956 Discovery of Transfer RNA
It was a small molecular weight, a low molecular weight RNA which we called soluble RNA and of course as we know now became known as transfer RNA and plays ...
[15]
https://www.genenames.org/data/genegroup/#!/group/478
[16]
Compilation of tRNA sequences and sequences of tRNA genes
Each tRNA or tRNA gene is specified by the (abbreviated) name of the organism from which it was isolated and a four digit code: the first three digits identify ...
[17]
Nomenclature - Prayag MURAWALA Lab
Apr 25, 2021 · Transfer RNAs should receive gene names following the pattern tRNA-XXX-YYY- GtRNAdbID, where XXX is the three-letter amino acid code, YYY is the ...
[18]
Aminoacyl-tRNAs: setting the limits of the genetic code
These include the eukaryotic elongator tRNAMet (but not tRNAi Met), all of which is then charged with methionine. A fraction of this Met-tRNAMet is then ...<|control11|><|separator|>
[19]
Systematic identification of tRNA genes in Drosophila melanogaster
Among the functional, cytosolic tRNAs decoding the 20 standard amino acids, each isoacceptor is encoded by between five (tRNA:His) and 26 (tRNA:Arg) genes, ...
[20]
Eukaryotic Initiator tRNA: Finely Tuned and Ready for Action - NIH
The initiator tRNA reads the start codon, allowing translation to begin in the correct location, and is tuned for the ribosomal P site.Missing: nomenclature | Show results with:nomenclature
[21]
Transfer RNA - an overview | ScienceDirect Topics
tRNA, or transfer RNA, is defined as a small RNA molecule, typically consisting of 70–90 nucleotides, that transports specific amino acids to the growing ...
[22]
Selenocysteine inserting tRNAs: an overview - Oxford Academic
Cytoplasmic elongators tRNAs of higher eukarya possess the canonical cloverleaf structure and display 26 invariant or semi-invariant nucleotides: U9, Y11, G18- ...
[23]
Synthetic Tyrosine tRNA Molecules with Noncanonical Secondary ...
The D and T loops are bound together by the invariant G18-ψ55 and G19-C56 base pairs (“ψ” is pseudouridine, a modified U), while the D stem and its surrounding ...
[24]
Structure of a Ribonucleic Acid - Science
Holley, R. W., Journal of Biological Chemistry 240: 2122 (1965). Web of ... Holley et al. ,. Structure of a Ribonucleic Acid.Science147,1462-1465(1965) ...
[25]
CCA Addition to tRNA: Implications for tRNA Quality Control - PMC
Upon folding of tRNA into an L shaped tertiary structure, the CCA sequence is placed at the end of the coaxially stacked acceptor stem and T stem. The acceptor ...
[26]
Transfer RNA - an overview | ScienceDirect Topics
The 2-D structure of tRNA, which is generally described by a cloverleaf model, consists of five elements: a CCA acceptor stem, a D (dihydrouridine)-loop, an ...
[27]
Transfer RNA (tRNA)- Definition, Structure, Processing, Types ...
Aug 3, 2023 · tRNA is only 70-90 nucleotides in length, making it the smallest out of the three main RNAs (mRNA and rRNA). The molecular weight of the ...What is tRNA? · Kinds of tRNA Structure · Composition of tRNA · Processing of tRNA
[28]
The G·U wobble base pair: A fundamental building block of RNA ...
The G·U wobble base pair is a fundamental unit of RNA secondary structure that is present in nearly every class of RNA from organisms of all three phylogenetic ...
[29]
TRANSFER RNA: MOLECULAR STRUCTURE, SEQUENCE, AND ...
The eight semi-invariant residues present in almost every tRNA active in protein synthesis are Y I h R15, R24, Y 32, H37, Y 48, R57, and Y 60' Most tRNAs.
[30]
Three-dimensional structure of yeast phenylalanine transfer RNA at ...
Mar 1, 1974 · At 3Å resolution, the electron density map of crystalline tRNA shows the polynucleotide chain as an alternating series of ribose and phosphate peaks.
[31]
Mg2+–RNA interaction free energies and their relationship ... - PNAS
Mg 2+ ions strongly stabilize RNA tertiary structures under conditions that only weakly affect RNA secondary structure stability.
[32]
Magnesium Contact Ions Stabilize the Tertiary Structure of Transfer ...
Dec 7, 2020 · Based on these studies, it is clear that magnesium ions are crucial for stabilizing the folded structure of tRNA. We present here a rigorous ...Introduction · Results · Discussion · Supporting Information
[33]
RNA modifications stabilize the tertiary structure of tRNA fMet by ...
Feb 7, 2022 · Here we show that the incorporation of the modified nucleotides in tRNA fMet from Escherichia coli leads to an increase in the local conformational dynamics.
[34]
The diverse structural modes of tRNA binding and recognition - NIH
The conserved tertiary organization of canonical tRNA arises through the formation of two orthogonal helices, consisting of the acceptor and anticodon domains.
[35]
Aminoacyl-tRNA synthetases - PMC - PubMed Central
Aminoacyl-tRNA synthetases (aaRSs) are universally distributed enzymes that catalyze the esterification of a tRNA to its cognate amino acid (i.e., the amino ...
[36]
Mechanisms and kinetic assays of aminoacyl‐tRNA synthetases
Jul 4, 2025 · The key players are aminoacyl-tRNA synthetases (AARSs), which read the genetic code by pairing cognate amino acids and tRNAs. AARSs establish ...Abstract · Two-step aminoacylation · Aminoacyl transfer · Post-transfer editing
[37]
Aminoacyl-tRNA synthetases and amino acid signaling
The aminoacylation of tRNAs by ARSs is a high-fidelity process usually composed of two steps. ARS activates their cognate amino acid using ATP, producing an ...
[38]
tRNA synthetase: tRNA Aminoacylation and beyond - PMC
The aminoacyl-tRNA synthetases (aaRSs) comprise an ancient family of enzymes that are responsible for the first step of protein synthesis.
[39]
Biochemistry of Aminoacyl tRNA Synthetase and tRNAs ... - Frontiers
This review provides information on AARSs and tRNA biochemistry, their role in the translation process, summarizes progress in cell-free engineering of tRNAs ...
[40]
The mechanism of discriminative aminoacylation by isoleucyl-tRNA ...
Dec 30, 2024 · The faithful charging of amino acids to cognate tRNAs by aminoacyl-tRNA synthetases (AARSs) determines the fidelity of protein translation.
[41]
Coordination between aminoacylation and editing to protect against ...
Sep 23, 2023 · Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes that ligate amino acids to tRNAs, and often require editing to ensure accurate protein ...
[42]
https://www.cell.com/trends/biochemical-sciences/fulltext/S0968-0004(03)00066-5
[43]
mRNA decoding in human is kinetically and structurally distinct from ...
Apr 5, 2023 · The decoding mechanism is both kinetically and structurally distinct from that of bacteria. Although decoding is globally analogous in both species.
[44]
Elongation factor-Tu can repetitively engage aminoacyl-tRNA within ...
Feb 5, 2020 · Elongation factor Tu (EF-Tu) facilitates rapid and accurate selection of aminoacyl-tRNA (aa-tRNA) by the bacterial ribosome during protein synthesis.
[45]
Decoding on the ribosome depends on the structure of the mRNA ...
Jul 2, 2018 · Our data suggest that the rigid nature of the mRNA backbone is important for ensuring efficient codon–anticodon interactions under suboptimal conditions.
[46]
Two proofreading steps amplify the accuracy of genetic code ... - PNAS
Nov 11, 2016 · We use tRNA mutants with different affinities for EF-Tu to demonstrate that proofreading of aa-tRNAs occurs in two consecutive steps. First, aa- ...
[47]
Novel base-pairing interactions at the tRNA wobble position crucial ...
Jan 21, 2016 · Posttranscriptional modifications at the wobble position of transfer RNAs play a substantial role in deciphering the degenerate genetic code on the ribosome.
[48]
The process of mRNA–tRNA translocation - PNAS
Translocation is the process that advances the mRNA–tRNA moiety on the ribosome, to allow the next codon to move into the decoding center.The Elongation Cycle, And... · Hybrid-State Trnas And... · The Gtp Hydrolysis Mechanism...
[49]
tRNA dynamics on the ribosome during translation - PNAS
Aug 18, 2004 · Conformational fluctuations of tRNA molecules reveal continuous, dynamic exchange between discrete configurations in pretranslocation and ...Trna Dynamics On The... · Sign Up For Pnas Alerts · Results
[50]
Structural basis of early translocation events on the ribosome - Nature
Jul 7, 2021 · How the ribosome hands the A-site tRNA to the P site during EF-G-catalyzed translocation. Science 345, 1188–1191 (2014). Article ADS CAS ...
[51]
Cell-specific differences in the requirements for translation quality ...
Protein synthesis has an overall error rate of approximately 10-4 for each mRNA codon translated. The fidelity of translation is mainly determined by two ...
[52]
Quality control of protein synthesis in the early elongation stage
May 17, 2023 · In the early stage of bacterial translation, peptidyl-tRNAs frequently dissociate from the ribosome (pep-tRNA drop-off) and are recycled by ...
[53]
The structural basis for release-factor activation during translation ...
Jun 12, 2019 · When the ribosome encounters a stop codon, it recruits a release factor (RF) to hydrolyze the ester bond between the peptide chain and tRNA.
[54]
Structure of the 70S ribosome bound to release factor 2 and ... - PNAS
We report the crystal structure of release factor 2 bound to ribosome with an aminoacyl tRNA substrate analog at the ribosomal P site, at 3.1 Å resolution.
[55]
Nonsense suppression in archaea - PNAS
Apr 27, 2015 · Nonsense suppression is defined as the read through of stop codons in an mRNA by a class of mutant tRNAs called nonsense suppressor tRNAs.
[56]
Engineered transfer RNAs for suppression of premature termination ...
Feb 18, 2019 · Here we present a high-throughput, cell-based assay to identify anticodon engineered transfer RNAs (ACE-tRNA) which can effectively suppress in-frame PTCs.
[57]
A Comprehensive tRNA Deletion Library Unravels the Genetic ...
Our tRNA deletion library contained 204 deletions out of the 275 nuclear-encoded tRNA genes identified in S. cerevisiae (see Materials and Methods). These ...
[58]
Enjoy the Silence: Nearly Half of Human tRNA Genes Are Silent - PMC
The human genome contains more than 500 tRNA genes to decode 61 codons. The reason for such a high genetic redundancy is to date unclear. As tRNA genes contain ...
[59]
RNA Polymerase III Advances: Structural and tRNA Functional Views
TFIIIC is a 6-subunit complex that recognizes the internal promoter elements of tRNA genes, the A and B boxes (Fig. 1). In chromatin, TFIIIC exhibits ...
[60]
Cellular dynamics of tRNAs and their genes - FEBS Press - Wiley
Nov 19, 2009 · In yeast ∼20% of the tRNA genes, encoding 10 different tRNAs, contain introns (Review: [23]). The introns range from 14 to 60 nucleotides and ...
[61]
Free introns of tRNAs as complementarity-dependent regulators of ...
Feb 11, 2025 · In humans, 7% of the approxi- mately 400 tRNA genes contain an intron, whereas in the yeasts. S. cerevisiae and Cryptococcus neoformans 22% (61/ ...
[62]
The mitochondrial tRNA conundrum - Nature
Jan 30, 2020 · The human mitochondrial genome encodes only 13 proteins, 2 ribosomal RNAs (rRNAs) and 22 mitochondrial transfer RNAs (tRNAs). All these genes are encoded ...
[63]
Evolution and structural variations in chloroplast tRNAs in ...
Oct 18, 2021 · The average number of chloroplast tRNA genes in each species was approximately 33. ... The number of tRNA genes in the chloroplast genome ...
[64]
Quantitative Analysis of Spatial Distributions of All tRNA Genes in ...
Summary of the 273 tRNA genes in budding yeast based on the Genomic tRNA Database was prepared based on the alignment of the tRNAs of Saccharomyces cerevisiae ...
[65]
The genomic loci of specific human tRNA genes exhibit ageing ...
May 11, 2021 · This study presents a comprehensive evaluation of the genomic DNA methylation state of human tRNA genes and reveals a discreet hypermethylation with advancing ...
[66]
Genomic organization of eukaryotic tRNAs
Apr 28, 2010 · Higher primates, for instance, have 616 ± 120 tRNA genes and pseudogenes of which 17% to 36% are arranged in clusters, while the genome of the ...
[67]
tRNA evolution from the proto-tRNA minihelix world - PMC
The Ac loop is found to be bracketed by 2–5-nt remnants of acceptor stems, which may have initially been able to pair (before LUCA; as a 31-nt minihelix).
[68]
Evolution of Life on Earth: tRNA, Aminoacyl-tRNA Synthetases and ...
Mar 2, 2020 · Because tRNA evolved from minihelices of known sequence, information is obtained about a minihelix world and a polymer world that preceded tRNA ...
[69]
The scenario on the origin of translation in the RNA world
Nov 27, 2010 · ... amino acids on the ribozyme facilitating their ligation. According to Hp4 and Hp14, proto-tRNAs was first involved in the RNA replication ...
[70]
Full article: Rooted tRNAomes and evolution of the genetic code
The mechanism for evolution of cloverleaf tRNA provides a root sequence for radiation of tRNAs and suggests a simplified understanding of code evolution. To ...
[71]
Expansion of Inosine at the Wobble Position of tRNAs, and Its Role ...
Dec 27, 2018 · L. 2018 . Codon adaptation to tRNAs with Inosine modification at position 34 is widespread among Eukaryotes and present in two Bacterial phyla.Abstract · Introduction · Results · Discussion
[72]
Gene transfer from organelles to the nucleus: Frequent and in big ...
This process, a special kind of lateral gene transfer called endosymbiotic gene transfer (3), appears to be very widespread in nature: ≈18% of the nuclear genes ...
[73]
Complete chemical structures of human mitochondrial tRNAs - Nature
Aug 28, 2020 · N6-threonylcarbamoyladenosine (t6A) is a bulky modification found at position 37 (3′ adjacent to the anticodon) of tRNAs responsible for codons ...
[74]
Epitranscriptomics: RNA Modifications in Bacteria and Archaea
Compared to other RNA species, tRNAs possess the highest number of RNA modifications, on average, 14 modifications per tRNA. A comparison of modified tRNA ...
[75]
Eukaryotic tRNAomes: Processing, Modification & Use
Transfer RNAs (tRNAs) contain sequence diversity beyond their anticodons and the large variety of nucleotide modifications found in all kingdoms of life.<|control11|><|separator|>
[76]
Deciphering the tRNA-derived small RNAs: origin, development ...
Dec 21, 2021 · During biogenesis, tRNAs are transcribed into precursor tRNAs (pre-tRNAs) via the action of RNA polymerase III. Then, pre-tRNAs are transformed ...Missing: history nomenclature sRNA
[77]
Full article: Novel insights into the roles of tRNA-derived small RNAs
There are two types of tsRNAs: tRNA-derived fragments (tRFs) and stress-induced tRNA halves (tiRNAs), which differ in their cleavage position.Introduction · Tsrnas Species And... · Tsrnas Involved In The...
[78]
tRNA-Derived Small RNAs: Biogenesis, Modification, Function and ...
Here, we review the current knowledge in regard to tsRNAs biogenesis, including the impact of RNA modifications on tRNA stability and discuss the existing ...
[79]
tRNA-derived small RNAs in human cancers: roles, mechanisms ...
Apr 15, 2024 · Recent studies have shown that tsRNAs play an important role in tumorigenesis by regulating biological behaviors such as malignant proliferation, invasion and ...Biogenesis Of Tsrnas · Tsrnas And Tumor Metastasis · Tsrnas And Metabolic...
[80]
tRNA-derived small RNAs (tsRNAs) in cardiovascular diseases
tsRNAs play important biological functions in these diseases, including the inhibition of apoptosis, epigenetic modification, intercellular signaling mediation, ...3.2 Tirnas: Stress-Induced... · 3.3 Rna-Seq And The... · 5.1 Tsrna And Mi
[81]
The function of tRNA-derived small RNAs in cardiovascular diseases
Jan 9, 2024 · This review provides a succinct overview of the characteristics, classification, and regulatory functions of tsRNAs in the context of CVDs.Mechanisms Of Tsrna Function · Regulating Mrna Translation · Tsrnas Functions In Cvds
[82]
Biogenesis, function, and landscape of tsRNAs in central nervous ...
Jul 11, 2023 · We describe the biogenesis and classification of transfer RNA-derived small RNAs (tsRNAs) and the effects of chemical modification of tRNA ...
[83]
Review Article tRNA-derived small RNAs in digestive tract diseases
This article aims to provide a comprehensive and up-to-date review of the classification and biological function of tsRNAs in gastrointestinal diseases.Review Article · Introduction · Biogenesis And...
[84]
Transcription by RNA polymerase III: insights into mechanism and ...
(i and ii) The internal box A and B elements present within tRNA genes (tDNA) are bound by the multiprotein TFIIIC complex. (iii) This recruits the TFIIB ...
[85]
Novel layers of RNA polymerase III control affecting tRNA gene ...
Feb 22, 2017 · The internally located A- and B-boxes are the main cis-acting control elements for transcription of tRNA genes (with the exception of the ...
[86]
Bacterial transfer RNAs - PMC - NIH
In addition, many bacterial transcripts are polycistronic in nature, containing more than one tRNA species (Li and Deutscher 2002; Ow and Kushner 2002). This ...
[87]
Ribonuclease P processes polycistronic tRNA transcripts in ... - NIH
Here we describe for the first time a previously unidentified pathway for the maturation of tRNAs in polycistronic operons (valV valW and leuQ leuP leuV) where ...
[88]
Generation of pre-tRNAs from polycistronic operons is the essential ...
We show here for the first time that the processing of RNase P-dependent polycistronic tRNA operons to release pre-tRNAs is the essential function of the ...
[89]
Structural basis of transfer RNA processing by bacterial minimal ...
Jul 1, 2025 · In the early steps of tRNA maturation, the endoribonuclease RNase P removes extra 5′ nucleotides (termed 5′-leader) from pre-tRNAs. RNase P is ...Results · Pre-Trna Recognition By... · Preparation Of Rnas For 3′...
[90]
to 5′ directional processing of dicistronic tRNA precursors by ...
Nov 28, 2018 · Subsequent endonucleolytic cleavage by the ribonucleoprotein enzyme ribonuclease P (RNase P) is responsible for removal of 5′ leader sequence to ...Results · Kinetics Of Rnase P... · A Stable Stem Loop In The...
[91]
tRNA maturation by the human mitochondrial RNase Z complex
Nov 8, 2024 · This study reveals its complete structural framework, detailing its role in tRNA maturation and substrate recognition, and provides insights into mitochondrial ...
[92]
New insights into RNA processing by the eukaryotic tRNA splicing ...
Through its role in intron cleavage, tRNA splicing endonuclease (TSEN) plays a critical function in the maturation of intron-containing pre-tRNAs.
[93]
Molecular mechanisms of template-independent RNA ...
Feb 17, 2014 · The universal 3′-terminal CCA sequence of tRNA is built and/or synthesized by the CCA-adding enzyme, CTP:(ATP) tRNA nucleotidyltransferase.
[94]
Evolution of tRNA nucleotidyltransferases: A small deletion ... - PNAS
Prominent members are tRNA nucleotidyltransferases (CCA-adding enzymes) with a unique template-independent mechanism of polymerization. These enzymes are ...
[95]
Quality Control Pathways for Nucleus-Encoded Eukaryotic tRNA ...
Apr 6, 2015 · We describe the known tRNA quality control processes that check tRNAs and correct or destroy aberrant tRNAs.Missing: misfolded | Show results with:misfolded
[96]
Surveillance and Cleavage of Eukaryotic tRNAs - MDPI
The nuclear surveillance pathway (Figure 1A) was discovered in temperature-sensitive yeast (Saccharomyces cerevisiae) strains lacking the tRNA methyl ...2.1. The Nuclear... · 2.2. The Rapid Trna Decay... · 3. Trna-Derived Fragments...
[97]
The yeast gene YNL292w encodes a pseudouridine synthase (Pus4 ...
In this paper we present experimental evidence showing that the protein encoded by the yeast YNL292w gene is tRNA:Ψ 55 synthase (Pus4). We have, therefore, ...
[98]
Mechanism of N-methylation by the tRNA m1G37 methyltransferase ...
Trm5 is a eukaryal and archaeal tRNA methyltransferase that catalyzes methyl transfer from S-adenosylmethionine (AdoMet) to the N1 position of G37 directly ...
[99]
Biosynthesis of wybutosine, a hyper‐modified nucleoside in ...
Wybutosine (yW) is a tricyclic nucleoside with a large side chain found at the 3′‐position adjacent to the anticodon of eukaryotic phenylalanine tRNA.
[100]
Queuosine‐modified tRNAs confer nutritional control of protein ...
Queuosine‐tRNA levels control the translation speed of queuosinylated‐tRNA decoded codons. •. Altered translation in the absence of queuosine results in ...
[101]
RNA modifying enzymes shape tRNA biogenesis and function - PMC
In this review, we summarize the known functions of tRNA modifying enzymes throughout the lifecycle of a tRNA molecule, from transcription to degradation.
[102]
Lost in Translation: Defects in Transfer RNA Modifications and ...
Post-transcriptional enzyme-catalyzed modification of tRNA occurs at a number of base and sugar positions and influences specific anticodon–codon interactions ...tRNA Modifications · Defects in tRNA Modifications... · Significance of Queuosine...
[103]
Queuosine tRNA Modification: Connecting the Microbiome to ... - NIH
Nov 26, 2024 · However, in eukaryotes, queuine (Q‐base), which is produced by gut microbiota and present in diet, is the precursor to Q synthesis by the tRNA‐ ...
[104]
Construction of two Escherichia coli amber suppressor genes - PNAS
Nonsense suppressors are alleles of tRNA genes altered in the anticodon, resulting in insertion of an amino acid in response to a termination codon.
[105]
[PDF] SUPPRESSORS IN ESCHERICHIA COLI* cellular component, the ...
This report presentsa general approach for the isolation of such recessive lethal suppressors and describes a new amber and a new ochre suppressor of this type.
[106]
Construction of Escherichia coli amber suppressor tRNA genes. II ...
Jun 20, 1990 · Using synthetic oligonucleotides, we have constructed 17 tRNA suppressor genes from Escherichia coli representing 13 species of tRNA.Missing: Su7 seminal
[107]
[PDF] A general approach for the generation of orthogonal tRNAs.
A general approach for the generation of orthogonal tRNAs. · Lei Wang, Peter G. Schultz · Published in Chemistry and Biology 1 September 2001 · Biology, Chemistry.<|control11|><|separator|>
[108]
A General Method for Site-specific Incorporation of Unnatural Amino ...
A new method has been developed that makes it possible to site-specifically incorporate unnatural amino acids into proteins.Missing: azide | Show results with:azide
[109]
Addition of p-azido-L-phenylalanine to the genetic code of ... - PubMed
We report the selection of a new orthogonal aminoacyl tRNA synthetase/tRNA pair for the in vivo incorporation of a photocrosslinker, p-azido-l-phenylalanine, ...Missing: paper | Show results with:paper
[110]
Versatility of Synthetic tRNAs in Genetic Code Expansion - PMC
Nov 7, 2018 · Each tRNA is highly processed, structured, and modified, to accurately deliver amino acids to the ribosome for protein synthesis. The tRNA ...
[111]
Biological evidence for the world's smallest tRNAs - PubMed
Aug 17, 2013 · Here, several tRNA genes are annotated that lack both the D- and the T-arm, suggesting even shorter transcripts with a length of only 42 nts.
[112]
Beyond the Canonical 20 Amino Acids: Expanding the Genetic ...
The orthogonal aaRS (red) aminoacylates the orthogonal tRNACUA (blue, red. CUA) with an unnatural amino acid (blue X) and does not cross-react with the.Missing: seminal | Show results with:seminal
[113]
Engineered tRNAs suppress nonsense mutations in cells and in vivo
May 31, 2023 · We showed that at PTCs that cause cystic fibrosis disease, an optimized suppressor tRNA alone restored protein expression and function, and ...
[114]
ACE-tRNAs are a platform technology for suppressing nonsense ...
Jul 12, 2025 · We provide evidence that anticodon-edited (ACE-) tRNAs efficiently suppress the most prevalent cystic fibrosis (CF)-causing PTCs, promoting ...
[115]
RARS2 Mutations: Is Pontocerebellar Hypoplasia Type 6 ... - PubMed
Mutations in the mitochondrial arginyl tRNA synthetase (RARS2) gene are associated with Pontocerebellar Hypoplasia type 6 (PCH6).
[116]
Further delineation of pontocerebellar hypoplasia type 6 due to ...
Pontocerebellar hypoplasia type 6 (PCH6) (MIM #611523) is a recently described disorder caused by mutations in RARS2 (MIM *611524), the gene encoding ...
[117]
RARS2 Mutations Cause Early Onset Epileptic Encephalopathy ...
We suggest that RARS2 gene mutations can cause a metabolic neurodegenerative disease manifesting primarily as EOEE with post-natal microcephaly.
[118]
Editing-defective tRNA synthetase causes protein misfolding and ...
Sep 7, 2006 · Here we demonstrate that low levels of mischarged transfer RNAs (tRNAs) can lead to an intracellular accumulation of misfolded proteins in neurons.
[119]
tRNA(Lys3): the primer tRNA for reverse transcription in HIV-1
tRNA(Lys3) is annealed to the viral RNA genome where it acts to prime the reverse transcriptase (RT)-catalyzed synthesis of viral DNA.
[120]
Role of tRNA modifications in human diseases - PubMed
Here, we have compiled current knowledge that directly link tRNA modifications to human diseases such as cancer, type 2 diabetes (T2D), neurological disorders, ...Missing: hypomodification | Show results with:hypomodification
[121]
A novel 3'tRNA-derived fragment tRF-Val promotes proliferation and ...
May 18, 2022 · A novel 3'tRNA-derived fragment tRF-Val was significantly upregulated in GC tissues and cell lines. tRF-Val expression was positively correlated with tumor ...
[122]
tRNA-derived fragment tRF-03357 promotes cell proliferation ...
Aug 16, 2019 · This study suggests that tRF-03357 might promote cell proliferation, migration and invasion, partly by modulating HMBOX1 in HGSOC.<|separator|>
[123]
Genetic Control of tRNA-Derived Fragments Contributes to Cancer ...
Aug 7, 2025 · Transfer RNA-derived fragments (tRFs) are a class of small non-coding RNAs that have exhibited several functions in cancer.
[124]
https://pubmed.ncbi.nlm.nih.gov/40773675/
[125]
External guide sequences targeting the aac(6')-Ib mRNA induce ...
Mar 26, 2007 · External guide sequences are short antisense oligoribonucleotides that induce RNase P-mediated cleavage of a target RNA by forming a precursor ...
[126]
Chemically modified tRNA enhances the translation capacity of ...
Aug 22, 2025 · 1b). Recently, AAV- or LNP-delivered engineered tRNAs have emerged as potential therapeutics for premature termination codons (PTC) diseases, ...
[127]
Decoding the general role of tRNA queuosine modification ... - Nature
Jan 2, 2025 · Transfer RNA (tRNA) contains modified nucleosides essential for modulating protein translation. One of these modifications is queuosine (Q), which affects NAU ...
[128]
Distinct fingerprints of tRNA-derived small non-coding RNA in ...
Our profiling of tsRNAs indicates disease-specific fingerprints in animal models of neurodegeneration, which require validation in human disease ...
[129]
Neurological Diseases Caused by Loss of Transfer RNA Modifications
Mar 10, 2025 · Loss of tRNA modifications can cause tRNA destabilization, altered decoding, or production of toxic tRNA fragments, which lead to the severely dysregulated ...
[130]
50 years ago protein synthesis met molecular biology: the ...
Oct 1, 2005 · Hoagland followed up this lead and found that the attachment of amino acids to this “soluble RNA” (soon renamed tRNA) seemed to be catalyzed by ...Missing: 1950s | Show results with:1950s
[131]
The Nobel Prize in Physiology or Medicine 1968 - NobelPrize.org
The Nobel Prize in Physiology or Medicine 1968 was awarded jointly to Robert W. Holley, Har Gobind Khorana and Marshall W. Nirenberg
[132]
Three-dimensional Tertiary Structure of Yeast Phenylalanine ...
The 3-angstrom electron density map of crystalline yeast phenylalanine transfer RNA has provided us with a complete three-dimensional model.
[133]
Wobble position modified nucleosides evolved to select ... - PubMed
This modified-wobble theory would be exemplified by a single codon recognition imposed on the anticodon by modification of the tRNA wobble position nucleoside.