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Polysome

A polysome, also known as a polyribosome, is a molecular complex formed by a single messenger RNA (mRNA) molecule bound to multiple ribosomes that simultaneously translate it into polypeptide chains, enabling the efficient synthesis of multiple protein copies from one mRNA transcript.^[1] This structure is fundamental to protein biosynthesis in both prokaryotic and eukaryotic cells, where it maximizes translational output by allowing ribosomes to queue along the mRNA without interference.^[2]^[3] Polysomes were first identified in the early 1960s through pioneering experiments using ultracentrifugation and radioactive labeling of amino acids in cell extracts, which revealed dense aggregates of ribosomes linked by mRNA rather than isolated particles. Originally termed "ergosomes," these findings, reported by Jonathan R. Warner, Paul M. Knopf, and Alexander Rich in 1963, demonstrated that the majority of protein synthesis occurs on such multi-ribosome structures, overturning earlier views of translation as a solitary ribosomal process and establishing the coding ratio of mRNA to proteins.^[4] Structurally, polysomes typically consist of 3 to 30 ribosomes spaced 80–100 nucleotides apart along the mRNA, often adopting linear, circular, or helical configurations to facilitate compact packing and coordinated translation; in mammalian cells, circular topologies predominate in the cytoplasm for enhanced stability and efficiency.^[3]^[5] Functionally, free polysomes in the cytosol produce cytoplasmic proteins, while those bound to the rough endoplasmic reticulum synthesize proteins destined for secretion, membranes, or organelles, playing critical roles in cellular responses such as synaptic plasticity in neurons where local polysome assembly supports rapid protein production during learning.^[2] Disruptions in polysome formation, often studied via polysome profiling, are linked to translational regulation under stress, development, and diseases like cancer, highlighting their dynamic role in gene expression control.^[6]^[7]

Overview

Definition

A polysome, also known as a polyribosome or ergosome, is a cluster of two or more ribosomes bound to a single messenger RNA (mRNA) molecule, enabling the simultaneous translation of that mRNA into multiple polypeptide chains during protein synthesis. The term "polysome" derives from "poly," indicating the multiple ribosomes involved, while "ergosome" was an earlier designation used in initial descriptions of these structures in the 1960s.^[2] This arrangement allows for efficient production of proteins by coordinating the decoding of the mRNA sequence across several ribosomes at once.^[3] In terms of composition, a polysome consists of one mRNA strand threaded through multiple ribosomes, with each ribosome occupying and protecting approximately 30-80 nucleotides of the mRNA, depending on the organism and specific conditions.^[8] This coverage reflects the ribosome's footprint on the mRNA, encompassing the region from the entry to the exit site of the transcript during elongation.^[9] Polysomes differ from monosomes, which are single ribosomes (such as the 80S particle in eukaryotes) typically not engaged in active translation or stalled on mRNA, whereas polysomes represent actively translating complexes that amplify protein output from limited mRNA resources.^[10] This mechanism for rapid protein production is conserved across both prokaryotic and eukaryotic cells, though prokaryotes often form polysomes more immediately after transcription due to coupled processes, while eukaryotes separate these steps spatially.^[2]

Historical Discovery

The discovery of polysomes began in the early 1960s, driven by efforts to understand the mechanism of protein synthesis following the identification of messenger RNA (mRNA). In 1963, Jonathan R. Warner, Paul M. Knopf, and Alexander Rich observed clusters of multiple ribosomes attached to a single mRNA molecule in extracts from HeLa cells using electron microscopy, revealing linear arrays of 4 to 6 ribosomes spaced approximately 100 Å apart.^[11] They termed these structures "polyribosomes," proposing that they represent functional units where several ribosomes simultaneously translate one mRNA to enhance protein production efficiency.^[11] Concurrently, Fritz O. Wettstein, Tibor Staehelin, and Hans Noll reported similar ribosomal aggregates in rabbit reticulocytes via sucrose gradient sedimentation and electron microscopy, introducing the term "ergosomes" to describe these mRNA-bound ribosome chains involved in hemoglobin synthesis.^[12] Shortly before these eukaryotic observations, biochemical evidence for polysome-like structures emerged in prokaryotes. In 1962, Robert W. Risebrough and colleagues demonstrated in Escherichia coli that newly synthesized, unstable RNA (later identified as mRNA) sediments with ribosomes in complexes containing multiple ribosomal units per RNA molecule, as shown by pulse-labeling experiments and analytical ultracentrifugation. This work established the existence of polysomes in bacteria, confirming their universal role across domains of life through sedimentation profiles revealing peaks corresponding to di-, tri-, and higher-order ribosome-mRNA aggregates. Subsequent electron microscopy studies in E. coli corroborated these findings, visualizing polysomal arrays analogous to those in eukaryotes.^[13] During the 1960s and 1970s, the terminology evolved from "ergosomes" to "polyribosomes" and eventually "polysomes" as structural and functional details became clearer through accumulating evidence.^[13] Warner et al.'s 1963 publication in Proceedings of the National Academy of Sciences became a seminal reference, linking polysomes directly to translation elongation by demonstrating that nascent polypeptide chains are distributed along the structure, consistent with sequential ribosome movement during protein synthesis.^[11] Follow-up studies, such as those by Warner and Rich in 1964, quantified the number of growing chains on reticulocyte polysomes, further solidifying the model of coordinated ribosomal transit on mRNA.

Structural Features

Prokaryotic Polysomes

Prokaryotic polysomes, also known as polyribosomes, represent clusters of multiple 70S ribosomes translating the same mRNA molecule in bacterial cells, characterized by their straightforward organization in the absence of nuclear membranes or other eukaryotic compartmentalization.^[9] This simplicity allows for rapid and efficient protein synthesis directly in the cytoplasm, where polysomes form without reliance on complex regulatory elements like those found in eukaryotes.^[14] The typical structure of prokaryotic polysomes features ribosomes arranged in double-row or sinusoidal configurations along the naked mRNA strand, enabling a compact assembly that maximizes translational efficiency.^[9] These arrangements often adopt a pseudohelical or staggered pattern, forming three-dimensional helical structures with diameters ranging from 40 to 100 nm, as observed in bacterial lysates and cells.^[15] Electron microscopy studies confirm this organization, revealing densely packed ribosomes in linear chains within the cytoplasm, unhindered by nuclear barriers.^[9] Ribosome spacing in these polysomes averages approximately 80 nucleotides of mRNA per ribosome, corresponding to a center-to-center distance of about 22-24 nm between adjacent ribosomes.^[14] Adjacent ribosomes typically orient in "top-to-top" or "top-to-bottom" configurations, with the 30S subunits facing each other to facilitate close packing along the mRNA.^[9] This spacing and orientation contribute to the overall compactness, allowing multiple ribosomes to progress simultaneously without significant steric interference. Unlike eukaryotic mRNAs, prokaryotic mRNAs lack a 5' cap and poly-A tail, enabling ribosomes to initiate translation directly at internal Shine-Dalgarno sequences located upstream of start codons.^[16] These sequences base-pair with the anti-Shine-Dalgarno region of the 16S rRNA in the 30S subunit, promoting efficient recruitment and polysome assembly without scanning from the 5' end. In bacteria such as Escherichia coli, polysomes are highly prevalent during active growth, comprising 70-90% of cellular ribosomes to support rapid protein production.^[17] This high proportion reflects the coupling of transcription and translation in prokaryotes, where polysomes dominate under exponential growth conditions.^[18] Cryoelectron tomography and transmission electron microscopy provide direct evidence of these compact, linear polysomal chains freely distributed in the bacterial cytoplasm, highlighting their role in unconstrained translational activity.^[9] In contrast to eukaryotic polysomes, which often involve more intricate spatial constraints, prokaryotic forms emphasize unencumbered, high-density organization.^[9]

Eukaryotic Polysomes

In eukaryotic cells, free cytoplasmic polysomes consist of multiple 80S ribosomes translating a single mRNA molecule characterized by a 5' 7-methylguanosine cap and a 3' poly-A tail, which facilitate ribosome recruitment and stability. Recent cryo-EM studies reveal that circular topologies are prevalent in mammalian cells, with most circular polysomes containing 4–8 ribosomes, while linear or helical forms can accommodate up to 33 ribosomes. These polysomes often exhibit helical or three-dimensional arrangements to optimize space in the crowded cytoplasm, such as left-handed supra-molecular helices with a diameter of approximately 58 nm, a pitch of 33 nm, and about 4 ribosomes per turn.^[5]^[19] In cell-free translation systems derived from eukaryotic sources, such as wheat germ extracts, polysomes can assemble into circular topologies; however, formation is largely independent of the 5' cap and 3' poly-A tail. This arrangement contrasts with the more open linear forms prevalent in some contexts and allows for compact, ring-like structures observed via electron microscopy. Cryo-electron microscopy (cryo-EM) and tomography studies reveal these structures as dynamic and flexible, with ribosomes loosely packed in pseudo-regular patterns that adapt to mRNA threading and elongation progression.^[20]^[21]^[5] Eukaryotic polysomes often exhibit a typical ribosome density of 1 per 80–100 nucleotides and inter-ribosome center-to-center distances of 20–40 nm. Polysome size and configuration vary across eukaryotic species, influenced by factors such as mRNA length and secondary structure; for instance, mammalian cells typically exhibit 4–8 ribosomes per polysome.^[19] Unlike prokaryotic polysomes with their simpler, naked mRNA chains, these eukaryotic adaptations support cap-dependent initiation in compartmentalized environments.^[19]

Membrane-Bound Polysomes

Membrane-bound polysomes, also known as rough endoplasmic reticulum (ER)-associated polysomes, are clusters of ribosomes attached to the cytoplasmic surface of the ER membrane, where they facilitate the co-translational translocation of proteins destined for secretion or membrane insertion. These polysomes form through the binding of individual ribosomes to mRNAs encoding secretory or membrane proteins, which contain N-terminal signal sequences recognized by the signal recognition particle (SRP). The SRP directs the ribosome-nascent chain complex to the Sec61 translocon on the ER membrane, anchoring the polysome via the emerging nascent polypeptide chain that threads through the translocon channel into the ER lumen.^[22] This attachment is solely mediated by the nascent chain and associated translocon components, without direct ribosome-membrane interactions beyond stabilizing elements like the ribosomal expansion segment ES27L.^[22] The structural organization of membrane-bound polysomes is constrained to a two-dimensional plane by the flat ER membrane, resulting in a more compact arrangement compared to free cytosolic polysomes. Cryo-electron tomography studies reveal that these polysomes often adopt chain-like or spiral conformations, with ribosomes packed at densities of approximately one ribosome per 80-100 nucleotides of mRNA, similar to free polysomes.^[22] This packing is facilitated by the planar geometry, which limits steric hindrance and promotes ordered arrays, sometimes visualized as rosette-like patterns in electron microscopy of cells like hepatocytes. In such cells, membrane-bound polysomes constitute 50-80% of total cellular polysomes, reflecting the high demand for secretory protein synthesis in specialized tissues.^[23]^[22] Upon completion of translation, the nascent protein is fully translocated or inserted into the ER, triggering dissociation of the ribosome from the translocon. This detachment allows the post-termination ribosome to recycle into the free cytosolic pool, where it can reinitiate translation on other mRNAs, maintaining cellular translation efficiency. The process involves release factors and GTPases that facilitate ribosome dissociation from the membrane, preventing prolonged occupancy of translocons.

Biogenesis and Assembly

Translation Initiation

In prokaryotes, translation initiation begins with the binding of the 30S ribosomal subunit to the mRNA at the Shine-Dalgarno (SD) sequence, a purine-rich motif located 4–9 nucleotides upstream of the start codon, through base-pairing with the complementary anti-SD sequence in the 3' end of 16S rRNA. This interaction is facilitated by initiation factors IF1, IF2 (bound to GTP and formylmethionyl-tRNA^fMet^), and IF3, which ensure accurate positioning of the initiator tRNA in the P site of the 30S subunit. Subsequently, the 50S subunit associates with the 30S initiation complex, triggering GTP hydrolysis by IF2, release of the initiation factors, and formation of the functional 70S ribosome ready for elongation.^[24] In eukaryotes, initiation involves the assembly of the 43S pre-initiation complex (PIC), consisting of the 40S small ribosomal subunit, eukaryotic initiation factors (eIFs) including eIF1, eIF1A, eIF3, and the eIF2-GTP-Met-tRNA_i^Met^ ternary complex. This 43S PIC is recruited to the 5' cap structure (m^7^GpppN) of the mRNA via the eIF4F complex, where eIF4E binds the cap and eIF4A (an RNA helicase) unwinds secondary structures in the 5' untranslated region (UTR) to enable scanning. The PIC scans downstream in a 5'-to-3' direction until it recognizes the start codon (AUG), typically embedded in the Kozak consensus sequence (GCCRCCAUGG, where R is a purine), which enhances recognition fidelity through interactions with the 40S subunit and eIFs.^[25] Key regulatory factors include eIF2, which forms the ternary complex with GTP and Met-tRNA_i^Met^ to deliver the initiator tRNA to the 40S subunit, and eIF4E, whose cap-binding activity is often limiting under cellular stress. Following start codon recognition, GTP hydrolysis by eIF5 (triggering eIF2 release) and subsequent joining of the 60S large subunit, catalyzed by eIF5B-GTP, complete monosome formation; this step involves additional GTP hydrolysis to release eIF5B and establish the 80S ribosome.^[25] Translation initiation is the rate-limiting step in protein synthesis, where its efficiency directly influences polysome density by determining the frequency of ribosome recruitment to mRNA. The initiation rate (k_init) can be approximated by the Michaelis-Menten equation k_init = [eIF2-GTP] / (K_m + [mRNA]), reflecting saturation kinetics dependent on eIF2-GTP availability and mRNA concentration.^[26] A fundamental distinction exists between prokaryotes, where ribosomes bind directly to the SD sequence near the start codon, and eukaryotes, which employ a scanning model starting from the 5' cap to locate the AUG.^[24]^[25]

Polysome Formation Mechanisms

Polysome formation occurs primarily during the elongation phase of translation, following the initiation of the first ribosome on the mRNA. As the leading ribosome progresses along the coding sequence, it exposes the 5' upstream region of the mRNA, enabling subsequent ribosomes to initiate translation and load onto the transcript. This sequential loading results in the assembly of multiple ribosomes into stable polysome clusters. The time required for a single ribosome to transit the entire coding sequence of a typical gene is approximately 50-100 seconds, influenced by the mRNA length and elongation kinetics.^[27] Ribosome spacing within polysomes is dynamically regulated to maintain efficient translation without steric hindrance. Adjacent ribosomes typically occupy positions separated by 80-100 nucleotides, accommodating the ribosome footprint of about 30 nucleotides while providing sufficient gaps to avoid collisions during movement. The ribosome itself exhibits helicase activity, actively unwinding secondary structures in the mRNA path—such as hairpins or stems—through mechanical force generated during translocation, ensuring smooth progression of the polysome array.^[5] At the termination phase, polysome integrity is preserved as individual ribosomes reach the stop codon independently. Release factors, such as RF1 or RF2 in prokaryotes and eRF1 in eukaryotes, recognize the stop codon, catalyze peptidyl-tRNA hydrolysis, and promote subunit dissociation from the mRNA. The resulting free ribosomes undergo recycling, often facilitated by factors like RF3 or ABCE1, allowing them to reinitiate on the same mRNA (if the 5' end remains accessible) or a new transcript, thereby sustaining polysome loading and turnover.^[28] A simple mathematical model describes polysome size as the number of ribosomes N ≈ L / d, where L represents the mRNA coding sequence length in nucleotides and d is the average spacing per ribosome (typically 80-100 nucleotides, encompassing the ~30-nucleotide footprint). This approximation highlights how longer mRNAs support larger polysomes, modulated by the elongation rate k_el of 5-20 amino acids per second, which determines transit speed and overall ribosome density. In eukaryotes, mRNA circularization—via interactions between the 5' cap-binding complex and 3' poly(A)-binding protein—facilitates rapid reinitiation of terminating ribosomes on the same transcript, enhancing polysome stability. Conversely, prokaryotic polycistronic mRNAs, encoding multiple genes in tandem, promote the formation of extended polysomes that translate successive open reading frames coordinately.^[29]^[27]^[30]^[31]

Functions in Translation

Enhancing Efficiency

Polysomes significantly enhance the efficiency of protein synthesis by enabling multiple ribosomes to translate a single mRNA molecule simultaneously, thereby amplifying the output of proteins from each transcript. In this arrangement, each ribosome operates independently along the mRNA, allowing concurrent production of multiple polypeptide chains without the need for additional mRNA transcription. For example, a polysome consisting of 10 ribosomes can achieve approximately 10-fold higher synthesis rates compared to a single monosome translating the same mRNA, as the collective elongation by multiple ribosomes accelerates overall protein yield. This mechanism is particularly crucial in cells requiring rapid protein production, where the density of ribosomes on mRNA directly scales with translational throughput.^[32] Beyond direct amplification, polysomes optimize resource utilization by reducing the risk of mRNA degradation, as ribosome occupancy shields transcripts from ribonucleases that target naked mRNAs. This protection extends mRNA half-life, permitting more translation cycles per transcript and conserving transcriptional energy. In bacteria under stress conditions, such as nutrient limitation or environmental challenges, polysomes sustain the synthesis of essential proteins, ensuring cellular viability without de novo mRNA production.^[33]^[34] The quantitative impact of polysomes is captured in the relationship where the rate of protein synthesis from an mRNA is given by polysome size × elongation rate (typically 5-20 codons per second in eukaryotes), leading to total yields of approximately 100–1000 proteins per mRNA depending on transcript length and cellular conditions. Experimental evidence from yeast mutants demonstrates that polysome abundance directly correlates with cellular growth rates, with higher polysome fractions observed in faster-growing strains, underscoring the efficiency gains.^[35]^[36] From an evolutionary perspective, polysomes confer an advantage by maximizing ribosome utilization and minimizing energy expenditure on redundant mRNA synthesis, as protein production consumes up to 40% of cellular ATP. This efficiency is prominently observed in rapidly dividing cells, such as early embryos, where elevated polysome formation supports burst-like protein synthesis essential for development.

Regulatory Roles

Polysomes play a central role in translational regulation by responding to cellular stress signals that modulate initiation rates and ribosome recruitment. During stress conditions such as viral infection or nutrient starvation, phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α) by kinases like PKR or GCN2 inhibits ternary complex formation, reducing global translation initiation and leading to polysome disassembly to conserve energy and redirect resources toward stress adaptation.^[37]^[38] This disassembly shifts mRNAs into non-translating pools, such as stress granules, while selectively allowing translation of stress-responsive transcripts.^[39] mRNA-specific regulatory elements further fine-tune polysome loading to control individual gene expression. Upstream open reading frames (uORFs) in the 5' untranslated region (UTR) often repress translation of the downstream main ORF by sequestering scanning ribosomes, resulting in reduced polysome association under basal conditions but enhanced translation during stress when eIF2α phosphorylation bypasses inhibitory uORFs.^[40] Internal ribosome entry sites (IRES) enable cap-independent initiation, allowing certain mRNAs to maintain or increase polysome occupancy when cap-dependent translation is impaired.^[41] Additionally, microRNAs (miRNAs) bound to target mRNAs promote rapid deadenylation via the CCR4-NOT complex, triggering decapping and eviction from polysomes, thereby silencing translation of specific transcripts.^[42] Signaling pathways integrate environmental cues to dynamically regulate polysome formation. The mechanistic target of rapamycin (mTOR) pathway, activated by growth factors and nutrients, phosphorylates 4E-binding proteins (4E-BPs), inhibiting their sequestration of eIF4E and thereby promoting cap-dependent recruitment of ribosomes to polysomes for mRNAs encoding growth-related proteins like cyclins and ribosomal components.^[43] In contrast, under nutrient limitation, mTOR inhibition reduces polysome loading on these transcripts. Dynamic remodeling of polysomes occurs in response to specific physiological signals, such as hypoxia, where hypoxia-inducible factors (HIFs) facilitate a shift toward IRES-driven translation. Hypoxia inhibits cap-dependent initiation via PERK-mediated eIF2α phosphorylation and mTOR suppression, but IRES-containing mRNAs like those for HIF-1α and VEGF maintain polysome association, enabling adaptive gene expression.^[44]^[45] This selective regulation can be conceptually modeled using a binding equilibrium for regulator effects on polysome occupancy:

\text{Fraction polysome-bound} = \frac{1}{1 + \frac{K_d}{[\text{regulator}]}}

where K_d is the dissociation constant and [\text{regulator}] reflects the concentration of activating or inhibitory factors influencing initiation.^[46] In developmental contexts, polysome gradients establish spatial patterns of translation. In Drosophila embryos, localized mRNA translation is controlled along anterior-posterior axes, with polysome profiling revealing stage-specific loading of maternal transcripts like nanos and oskar to direct patterning, independent of transcriptional changes.^[47]^[48]

Experimental Techniques

Classical Polysome Profiling

Classical polysome profiling, a foundational technique for studying translation, involves isolating ribosomal complexes from cell lysates and separating them based on sedimentation coefficients using sucrose density gradient ultracentrifugation. This method was first established in the early 1960s to visualize aggregates of ribosomes associated with mRNA, demonstrating their role in protein synthesis.^[11] In the original protocol, cell lysates from rabbit reticulocytes were prepared by gentle lysis to preserve polysomal integrity, followed by layering onto linear sucrose gradients (typically 15-30%) and centrifugation at high speeds (e.g., 25,000-40,000 rpm for 2-4 hours at 4°C) in swinging-bucket rotors.^[11] To prevent ribosome runoff during extraction, modern adaptations routinely incorporate translation elongation inhibitors such as cycloheximide (100 μg/mL) added to cells 5-10 minutes prior to lysis, freezing polysomes in place.^[49] Lysis buffers often include detergents like NP-40 or Igepal CA-630 (0.5-1%), along with salts (e.g., 100-150 mM KCl, 5-10 mM MgCl₂) and RNase inhibitors to maintain structure, followed by clarification of the lysate by low-speed centrifugation to remove nuclei and debris.^[50] During fractionation, the gradient is pumped from the bottom while monitoring ultraviolet (UV) absorbance at 254 nm or 260 nm to detect ribosomal species as they elute.^[49] Free 40S small subunits appear as a light peak near the top, followed by 60S large subunits, 80S monosomes (initiated but not elongating ribosomes), and progressively heavier peaks corresponding to di-, tri-, tetra-, and higher-order polysomes sedimenting further down the gradient.^[11] The absorbance trace provides a visual "polysome profile," where the ratio of polysome area to monosome/subunit area indicates global translation efficiency; for instance, a shift toward heavier fractions suggests increased polysome formation under active synthesis conditions.^[50] Fractions are collected (e.g., 12-20 across the gradient) and can be flash-frozen for storage. Protocols using 10-50% sucrose gradients have become standard for mammalian cells, offering better resolution of polysome peaks compared to earlier 15-30% ranges. Post-fractionation analysis typically involves RNA extraction from individual or pooled fractions using phenol-chloroform or column-based kits, followed by quantification of specific mRNAs via quantitative PCR (qPCR) or, in more recent refinements, RNA sequencing to assess transcript distribution.^[49] mRNAs predominantly in heavy polysome fractions (>3 ribosomes per mRNA) are considered actively translated, while those in subpolysomal fractions indicate repression or low efficiency. This allows measurement of global translation rates, such as the percentage of total mRNA engaged in polysomes, providing insights into cellular responses to stress or stimuli. For example, in mammalian systems, protocols refined in the 2000s improved yield and reproducibility for tissue samples by optimizing buffer compositions and incorporating protease inhibitors.^[50] Despite its utility, classical polysome profiling captures only a static snapshot of translation at the moment of fixation, missing dynamic changes over time.^[49] It is also sensitive to preparation artifacts, such as incomplete inhibition leading to polysome disassembly or non-specific co-sedimentation of mRNA-ribonucleoprotein complexes, which can be partially addressed by controls like puromycin dissociation.^[49] The technique's reliance on ultracentrifugation equipment limits throughput, though it remains a gold standard for validating translation states due to its direct visualization of ribosomal distributions.^[50]

Advanced Methods and Analysis

Ribosome profiling, also known as Ribo-seq, represents a significant advancement in polysome analysis by enabling nucleotide-resolution mapping of ribosome positions across the transcriptome. The method involves treating cell lysates with micrococcal nuclease (MNase) to digest unprotected RNA, leaving ribosome-protected fragments (RPFs) of approximately 28-30 nucleotides that correspond to the ribosome footprint. These fragments are then isolated, reverse-transcribed, and subjected to deep sequencing, allowing precise determination of ribosome occupancy and translation dynamics at single-codon resolution. This technique, first detailed in seminal work, has revolutionized the study of the translatome by quantifying ribosome density and identifying regulatory elements such as upstream open reading frames (uORFs).^[51]^[52] Polysome-seq extends classical polysome profiling by incorporating high-throughput sequencing of RNA from fractionated gradients, providing genome-wide insights into translational states. Variants of Polysome-seq often involve parallel analysis of light (subpolysomal) and heavy (polysomal) fractions to distinguish non-translating from actively translating mRNAs, enabling differential quantification of ribosome association. To address challenges in cross-species or condition-specific comparisons, spike-in controls—such as exogenous mRNAs from evolutionarily distant organisms—are incorporated during lysis and fractionation, facilitating normalization of sequencing depths and mitigating biases from varying ribosome loading efficiencies. This approach enhances the accuracy of translatome comparisons across samples, revealing subtle shifts in translational regulation.^[53]^[54] Computational tools are essential for processing and interpreting the vast datasets generated by these sequencing-based methods. RiboGalaxy, a Galaxy-based web platform, streamlines Ribo-seq analysis through integrated workflows for quality control, read alignment to reference genomes, and visualization of ribosome footprints, making it accessible for non-specialists while supporting custom parameter adjustments. For polysome profiles, transformation clustering algorithms apply mathematical transformations to absorbance traces from sucrose gradients, enabling automated detection and quantification of polysome peaks corresponding to specific ribosome numbers (e.g., monosomes, disomes). These tools improve reproducibility by reducing manual intervention and facilitating the identification of translational shifts in large-scale experiments.^[55]^[56] Recent advances since 2020 have further refined polysome techniques for high-resolution functional genomics. Massively parallel polyribosome profiling, for instance, uses barcoded reporter libraries to simultaneously assess thousands of UTR variants, identifying those that alter polysome distribution and translational output, with enrichment for pathogenic mutations in neurodevelopmental genes. Additionally, puromycin-based labeling methods, such as pSNAP, incorporate puromycin analogs to tag nascent polypeptide chains on polysomes, allowing affinity purification and mass spectrometry-based detection of translating proteins without disrupting gradient fractionation. These innovations enable the dissection of variant-specific translational defects and real-time monitoring of nascent chain synthesis in complex biological contexts.^[57]^[58] Integration of polysome data with proteomics provides a multi-omics view of translation, linking mRNA-level changes to protein abundance. Translational efficiency (TE), a key metric, is calculated as the ratio of sequencing reads from polysome-bound mRNA to total cellular mRNA reads, quantifying the proportion of transcripts actively translated:

\text{TE} = \frac{\text{polysome-bound mRNA reads}}{\text{total mRNA reads}}

This formula, applied post-normalization, reveals discrepancies between transcription and protein output, as validated in diverse cellular models. Combining TE with proteomic measurements, such as mass spectrometry of puromycin-labeled nascent chains, elucidates post-transcriptional regulatory mechanisms and enhances predictive models of proteome dynamics.^[20]^[53]

Biological and Pathological Significance

In Cellular Processes

Polysomes play a crucial role in cellular development, particularly in oocytes where maternal mRNAs are stored in a translationally repressed state during oogenesis. In Xenopus laevis, these mRNAs, such as those encoding BMP signaling proteins, are sequestered away from polysomes in the oocyte, ensuring that embryonic development relies on post-transcriptional control rather than new transcription. Upon fertilization, specific maternal mRNAs are rapidly recruited onto polysomes, enabling localized translation that supports early embryogenesis and patterning.^[59]^[60]^[61] During the cell cycle, polysome dynamics are tightly coordinated with proliferative phases to meet biosynthetic demands. In G1/S transition, polysome expansion occurs, enhancing the translation of mRNAs encoding ribosomal proteins and other biosynthetic machinery to support cell growth and DNA replication. This increase in polysome loading correlates with elevated overall translation rates, facilitating the production of proteins necessary for progression into S phase. Conversely, during mitosis, polysomes disassemble or translation arrests, with ribosomes stalling to prevent errors in chromosome segregation and ensure orderly division.^[62]^[63]^[64] In stress adaptation, the integrated stress response (ISR) remodels polysomes to prioritize survival under adverse conditions like nutrient deprivation or ER stress. Phosphorylation of eIF2α by ISR kinases globally reduces polysome formation, inhibiting cap-dependent translation of most mRNAs while selectively enhancing the translation of ATF4 via its upstream open reading frames. This polysome shift allows ATF4 to drive the expression of genes involved in amino acid metabolism and antioxidant defense, promoting cellular resilience. Polysome profiling confirms that ATF4 mRNA association with ribosomes increases during ISR activation, underscoring its role in adaptive reprogramming.^[65]^[66]^[67] Polysomes in neurons are localized to dendrites, enabling activity-dependent local translation essential for synaptic plasticity. These dendritic polysomes translate mRNAs encoding proteins like PSD-95 and CaMKII, which are critical for long-term potentiation and structural remodeling of synapses. Imaging and profiling studies reveal that synaptic stimulation triggers polysome assembly at activated sites, allowing rapid, localized protein synthesis without reliance on somatic transcription. This mechanism supports learning and memory by fine-tuning synaptic strength in response to neural activity.^[68]^[69]^[70] In hepatic homeostasis, diurnal polysome shifts regulate the translation of metabolic enzymes to align with daily feeding-fasting cycles. Ribosome and polysome profiling in mouse liver shows rhythmic changes in translatome composition, with increased polysome loading of mRNAs for glycolytic and lipogenic enzymes during the active (dark) phase when nutrients are processed. Conversely, fasting-associated mRNAs for gluconeogenesis and fatty acid oxidation show peak translation in the rest (light) phase. These oscillations, driven by circadian clock components, ensure efficient energy homeostasis and prevent metabolic imbalances.^[71]^[72]^[73]

Implications in Disease and Research

Dysregulation of polysome formation and function plays a central role in cancer progression, particularly through hyperactivation of the mTOR pathway, which enhances the translation of oncogenic mRNAs such as c-Myc. In many cancers, mTOR signaling drives the assembly of larger polysomes on these transcripts, promoting rapid synthesis of proteins that support cell proliferation and survival.^[74] For instance, studies have shown that mTOR-dependent phosphorylation facilitates c-Myc mRNA recruitment to polysomes, amplifying oncogene expression in tumors like lymphomas and multiple myelomas.^[75] Ribosome profiling techniques, including Ribo-seq, have revealed translational vulnerabilities in these polysome-dependent pathways, identifying targets for therapies that selectively inhibit cancer-specific translation without broadly disrupting host protein synthesis.^[76] In neurodegenerative diseases, polysome alterations contribute to protein synthesis defects and neuronal dysfunction. In Huntington's disease, mutant huntingtin leads to compacted polysome structures in neurons, causing ribosome stalling and reduced global translation efficiency, which exacerbates polyglutamine aggregation and toxicity.^[77] Similarly, in amyotrophic lateral sclerosis (ALS), TDP-43 mutations or mislocalization reorganize polysomes, shifting profiles toward larger complexes while impairing the translation of specific mRNAs involved in motor neuron maintenance; this results in decreased protein output and contributes to disease pathology.^[78] These changes highlight how polysome dysregulation disrupts the balance of neuroprotective versus neurotoxic proteins in affected brain regions.^[79] Viruses exploit host polysomes to prioritize their own protein production, often outcompeting cellular mRNAs during infection. Vesicular stomatitis virus (VSV), for example, recruits host polysomes to translate viral capsid and envelope proteins by enhancing the association of its mRNAs with heavy polysome fractions, while simultaneously suppressing host translation through phosphorylation of initiation factors.^[80] This hijacking mechanism allows VSV to rapidly produce structural components essential for virion assembly, demonstrating how polysome dynamics can be subverted for viral replication.^[81] Therapeutic strategies targeting polysome assembly offer promise for both antiviral and antitumor applications. Inhibitors like rocaglamide disrupt eIF4A helicase activity, preventing the formation of productive polysomes on structured viral and oncogenic mRNAs, thereby selectively halting translation of targets such as SARS-CoV-2 proteins or c-Myc-driven transcripts with minimal impact on housekeeping genes.^[82] This approach has shown efficacy in preclinical models, extending survival in MYC-overexpressing lymphomas and inhibiting replication of RNA viruses including flaviviruses.^[83] Advances in polysome profiling during the 2020s have illuminated the role of untranslated region (UTR) mutations in pathogenesis, enabling the identification of variants that shift polysome occupancy and alter translation rates. Massively parallel assays have detected pathogenic UTR mutations—enriched in neurodevelopmental disorders—that reduce polysome loading on critical mRNAs, providing insights into disease mechanisms and potential diagnostic markers.^[84] Additionally, spike-in normalization methods have extended polysome profiling to limited samples from small tissues or biobanks, facilitating quantitative analysis of translational changes in rare cell types or frozen clinical specimens without bias from low RNA yields.^[85] These innovations underscore the utility of polysome studies in uncovering translational dysregulation across diseases.

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Jan 31, 2020 · During protein synthesis, multiple ribosomes can form a structure known as a polysome, which produces multiple protein copies from a single mRNA ...Missing: distinction | Show results with:distinction
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A MULTIPLE RIBOSOMAL STRUCTURE IN PROTEIN SYNTHESIS | PNAS
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[12]
https://www.nature.com/articles/197430a0
[13]
https://www.cell.com/trends/biochemical-sciences/fulltext/S0968-0004(02)02126-6
[14]
Translation initiation in bacterial polysomes through ribosome ...
Apr 9, 2018 · During translation, consecutive ribosomes load on an mRNA and form a polysome. The first ribosome binds to a single-stranded mRNA region and ...
[15]
[PDF] The Structural and Functional Organization of Ribosomal ...
Nov 13, 2018 · shows a very compact helical structure with about four ribosomes per turn [15]. ... ultrathin (~40-100 nm) sections of Thermus thermophilus 70S ...Missing: diameter | Show results with:diameter
[16]
From RNA to Protein - Molecular Biology of the Cell - NCBI Bookshelf
The mRNA is then pulled through the ribosome; as its codons encounter the ribosome's active site, the mRNA nucleotide sequence is translated into an amino acid ...<|separator|>
[17]
Fraction of active ribosomes - Bacteria Escherichia coli - BNID 102344
563 bottom paragraph: "The fraction of ribosomes which are actively engaged in peptide synthesis at a given moment was estimated by sucrose gradient analysis, ...
[18]
Fraction of ribosomes synthesizing protein as a function of ... - PubMed
Both measurements showed that the fraction of ribosomes synthesizing protein increased with specific growth rate, from 30 to 70% over the range studied.Missing: polysomes | Show results with:polysomes
[19]
Polyribosomes of circular topology are prevalent in mammalian cells
Dec 30, 2022 · Even in early electron microscopy studies, it was found that polyribosomes in eukaryotic cells can take a variety of shapes (3–13).
[20]
Improved Ribosome-Footprint and mRNA Measurements Provide ...
Feb 23, 2016 · Studies using microarrays for global polysome profiling indicate that ribosome densities for different mRNAs vary over a 100-fold range ...
[21]
Step-wise formation of eukaryotic double-row polyribosomes ... - NIH
We found that polysome formation is a long process, requiring many rounds of translation that proceeds via distinct phases, starting from short linear polysomes ...Missing: composition | Show results with:composition<|control11|><|separator|>
[22]
https://doi.org/10.1016/j.str.2012.06.010
[23]
Translation in Prokaryotes - PMC - PubMed Central
This review summarizes our current understanding of translation in prokaryotes, focusing on the mechanistic and structural aspects of each phase of translation: ...
[24]
THE MECHANISM OF EUKARYOTIC TRANSLATION INITIATION ...
On most mRNAs, 48S complexes form by the “scanning” mechanism: a 43S preinitiation complex (comprising a 40S subunit, the eIF2–GTP–Met-tRNAMeti ternary complex ...
[25]
Polysome Fractionation and Analysis of Mammalian Translatomes ...
May 17, 2014 · mRNPs, monosome (80S) and polysome fractions were separated using the polysome fractionation method. ... This important distinction between ...
[26]
Control of translation initiation: a model-based analysis from limited ...
We have built a detailed kinetic model of translation initiation in yeast and have used a novel approach to determine the flux controlling steps based on ...
[27]
Interpreting ribosome dynamics during mRNA translation - PMC
The elongation is a complex polymerization process, where the ribosome moves along the mRNA while reading one codon (three nucleotides) at a time through the ...Missing: polysome spacing
[28]
The Ribosome Uses Two Active Mechanisms to Unwind mRNA ...
The unwinding mechanisms revealed in our studies serve as a quantitative basis for understanding how elongation rates are regulated by structured mRNAs. What ...
[29]
Dynamics of ribosomes and release factors during translation ... - eLife
Jun 11, 2018 · Release factors RF1 and RF2 promote hydrolysis of peptidyl-tRNA during translation termination. The GTPase RF3 promotes recycling of RF1 and RF2.Missing: membrane- polysomes detachment
[30]
Gene length as a regulator for ribosome recruitment and protein ...
Dec 12, 2017 · We explain how the transcript length may play a central role in establishing ribosome recruitment and the overall translation rate of an mRNA.
[31]
Single-molecule visualization of mRNA circularization during ...
Jan 31, 2023 · Most mRNAs are circularized via the eIF4E–eIF4G–PABP interaction, which stabilizes mRNAs and enhances translation by recycling ribosomes.
[32]
Polysome - an overview | ScienceDirect Topics
Polysomes are structures formed when multiple ribosomes translate a single mRNA, facilitating efficient protein synthesis. They are also known as polyribosomes.
[33]
Ribosome in action: Translational efficiency and protein folding
Both translation initiation and elongation contribute to the frequency of ribosome loading in polysomes, which can further change translational efficiency.
[34]
The intimate relationships of mRNA decay and translation - PMC
Consistent with this notion, mRNAs with shortened poly(A) tails only appear to leave polysomes and become targeted to P-bodies when Dhh1, Pat1, and other ...
[35]
Coping with stress: How bacteria fine-tune protein synthesis ... - NIH
In response to stress conditions or nutrient depletion, bacterial cells reduce ribosome biogenesis, modify ribosomes and components of the translational ...
[36]
Yeast 18 S rRNA Is Directly Involved in the Ribosomal Response to ...
The plot of the fraction of ribosomes found in polysome fractions (calculated from the P/M ratio) against the growth rate (times doubling/h) of each mutant ...
[37]
Role of eIF2α Kinases in Translational Control and Adaptation to ...
Phosphorylation of eIF2α causes inhibition of global translation, which conserves energy and facilitates reprogramming of gene expression and signaling pathways ...
[38]
A little less aggregation a little more replication: Viral manipulation of ...
Jun 16, 2022 · Activation of these kinases initiates the ISR by phosphorylation of eIF2α leading to translation inhibition, polysome disassembly, and the ...
[39]
Molecular mechanisms of stress granule assembly and disassembly
In most physiological cases, translation inhibition is initiated through phosphorylation of eIF2α by one or more of the four eIF2α kinases: PKR, PERK/PEK, HRI ...
[40]
Upstream Open Reading Frames Differentially Regulate Gene ...
This review presents key features of uORFs that serve to optimize translational control that is essential for regulation of cell fate in response to ...Ribosome Bypass In The Isr · Ribosome Bypass Is Dependent... · Ribosome Bypass And...Missing: paper | Show results with:paper
[41]
A New Framework for Understanding IRES-mediated Translation
This review seeks to set the basic ground rules for the analysis of different initiation pathways that are associated with these new mRNAs.3. Problematic Mrna... · 4. Ires-Mediated Translation · A. Ure2 MrnaMissing: paper | Show results with:paper
[42]
Deadenylation is a widespread effect of miRNA regulation - PMC - NIH
We show that ∼60% of AGO1 targets are regulated by CAF1 and/or NOT1, indicating that deadenylation is a widespread effect of miRNA regulation.Missing: eviction | Show results with:eviction
[43]
The mTOR Pathway in the Control of Protein Synthesis | Physiology
Through a component of mTORC1 (raptor), mTOR brings about the phosphorylation of targets such as 4E-BP1 and the S6 kinases. Certain agents act through ERK ...
[44]
Hypoxia-inducible Factor-1α mRNA Contains an Internal Ribosome ...
These data indicate that the presence of an IRES in the HIF-1α 5′UTR allows translation to be maintained under conditions that are inhibitory to cap-dependent ...
[45]
Hypoxia-mediated Selective mRNA Translation by an Internal ...
To test the theory that mRNAs important in the adaptive response to low O2 were selectively translated in an IRES-dependent manner, we analyzed a panel of ...Missing: driven | Show results with:driven
[46]
[PDF] Equations for Steady-State Equilibrium Binding
You can now write the equation in terms of the fraction (fB) of BT bound in the AB complex: (8). This is the equation for a hyperbola. Remember, AT must be ...Missing: polysome regulator
[47]
Global analyses of mRNA translational control during early ...
To understand post-transcriptional regulation during Drosophila early embryonic development, we used sucrose polysomal gradient analyses and GeneChip analysis ...
[48]
Setting the stage for development: mRNA translation and stability ...
Feb 9, 2005 · This review focuses on the mechanisms and functions of regulated maternal mRNA translation and stability in Drosophila
[49]
Analysis of translation using polysome profiling - Oxford Academic
Polysome profiling has been developed to infer the translational status of a specific mRNA species or to analyze the translatome.Missing: ergosome | Show results with:ergosome
[50]
Efficient analysis of mammalian polysomes in cells and tissues ...
Aug 10, 2018 · We also combine Ribo Mega-SEC with downstream electron microscopy and high-throughput proteomic analysis to characterize isolated polysomes.
[51]
Genome-Wide Analysis in Vivo of Translation with Nucleotide ...
Apr 10, 2009 · Ribosome profiling reports on the precise positions of ribosomes, making it possible to delineate what parts of a transcript are being decoded.
[52]
Simple and inexpensive ribosome profiling analysis of mRNA ... - NIH
Jul 8, 2015 · We provide a simplified ribosome profiling method that uses micrococcal nuclease to generate ribosome footprints in crude cellular extracts.Missing: seminal | Show results with:seminal
[53]
Analysis of translation using polysome profiling - PMC - NIH
Oct 7, 2016 · Polysome profiling is based on sucrose-gradient separation of translated mRNAs, which are associated with polysomes, from untranslated ones.Missing: size formula
[54]
Normalized Ribo-Seq for Quantifying Absolute Global and Specific ...
Feb 20, 2022 · The use of an evolutionarily distant species as spike-in has already been successfully applied to normalize Ribo-Seq datasets in different ...
[55]
RiboGalaxy: A browser based platform for the alignment, analysis ...
Jan 29, 2016 · Ribosome profiling (ribo-seq) is a technique that uses high-throughput sequencing to reveal the exact locations and densities of translating ...Results · Using Ribogalaxy · Figure 1
[56]
transformation clustering algorithm and its application in ...
Jul 11, 2022 · We optimized this algorithm for the detection and profiling of polyribosomes, which play both constitutive and regulatory roles in gene expression.Missing: peak | Show results with:peak
[57]
Massively Parallel Polyribosome Profiling Reveals Translation ...
Aug 27, 2024 · To determine variants that changed polysome distribution, we used read counts in polysome fractions to build a negative binomial generalized ...
[58]
Proteome-wide analysis of elongating nascent polypeptide chains
Jul 15, 2022 · We describe pSNAP, a method for proteome-wide profiling of NPCs by affinity enrichment of puromycin- and stable isotope-labeled polypeptides.
[59]
Polyribosome analysis for investigating mRNA translation in ... - NIH
Figure 2. The polyribosome association of maternal mRNAs encoding proteins of the BMP signaling pathway is regulated during oocyte maturation and embryogenesis.
[60]
Mobilization of specific maternal RNA species into polysomes after ...
We have examined the accumulation of nonpolysomal maternal RNAs in polysomes after fertilization in Xenopus laevis by measuring the distributions of specific ...Missing: post- | Show results with:post-
[61]
Poly(A) elongation during Xenopus oocyte maturation is required for ...
Abstract. Xenopus oocytes contain several mRNAs that are mobilized into polysomes only at the completion of meiosis (maturation) or at specific times ...
[62]
CDK Phosphorylation of Translation Initiation Factors Couples ...
Dec 11, 2018 · Protein translation in eukaryotes is cell-cycle dependent, with translation rates more robust in G1 phase of the cell cycle than in mitosis.
[63]
Regulation of mRNA translation during mitosis - PubMed Central - NIH
Aug 25, 2015 · ... cell cycle, specifically from G1 to S or G2. On the other hand ... polysomes and remain active during mitosis (Qin and Sarnow, 2004).
[64]
Polysome Translational State during the Cell Cycle - FEBS Press
The ratio of polysomes to single ribosomes was calculated from these figures. Labelling of Total Cell Proteins. At hourly intervals throughout the cell cycle. 5 ...
[65]
Analysis of Translational Control in the Integrated Stress Response ...
In this chapter, we focus on polysome profiling as a tool for establishing and characterizing translation control induced by eIF2 phosphorylation during ...
[66]
Translation reinitiation at alternative open reading frames regulates ...
Translation reinitiation at alternative open reading frames regulates gene expression in an integrated stress response ... ATF4 over the inhibitory uORF2 ...
[67]
The integrated stress response | EMBO reports
During stressful conditions, elevated translation of ATF4 mRNA facilitates transcriptional upregulation of stress‐responsive genes. ATF4 regulates the ...Missing: polysome | Show results with:polysome
[68]
Neuronal ribosomes exhibit dynamic and context-dependent ...
Oct 21, 2021 · Neurons use the translation of distally localized messenger RNAs (mRNAs) for synapse formation, axon growth, and synaptic plasticity. Although ...<|control11|><|separator|>
[69]
The prevalence and specificity of local protein synthesis during ...
Sep 17, 2021 · Hence, local sites of protein synthesis congregate near synapses along dendrites, giving rise to ~2 translational sites per synapse. The ...Results · Materials And Methods · Metabolic Labeling With Aha...
[70]
The Coordination of Local Translation, Membranous Organelle ...
Jul 14, 2021 · Local translation is clearly imperative for proper synaptic function and plasticity, and mRNAs encoding synaptic proteins are localized to and ...Rna Trafficking To Remote... · Transport Of Mrna To Remote... · Mirnas Fine-Tune Local...
[71]
Ribosome profiling reveals the rhythmic liver translatome and ...
We have used ribosome profiling in mouse liver to measure the translation of mRNAs into protein around the clock and at high temporal and nucleotide resolution.
[72]
Calorie restriction reprograms diurnal rhythms in protein translation ...
Dec 19, 2018 · To extend the knowledge on the molecular mechanisms of CR and circadian clock interaction, we performed polysome profiling in the liver of mice ...
[73]
Daily rhythms in hepatic polysome profiles and tyrosine ... - PubMed
Hepatic polysome profiles vary in untreated rats as a function of time of day. The ratio of polysomes to total ribosomes increases from 50 to 73 per cent in ...
[74]
Myc and mTOR converge on a common node in protein synthesis ...
Jun 26, 2013 · Here, we uncover a surprising and important functional link between Myc and mammalian target of rapamycin (mTOR)-dependent phosphorylation of ...Missing: polysomes | Show results with:polysomes
[75]
CRITICAL ROLE FOR CAP-INDEPENDENT C-MYC TRANSLATION ...
Oct 1, 2022 · Dysregulated c-myc is a determinant of multiple myeloma (MM) progression. Translation of c-myc can be achieved by an mTOR-mediated, cap-dependent mechanism or ...
[76]
c-MYC regulates mRNA translation efficiency and start-site selection ...
May 29, 2019 · We show that MYC alters the efficiency and quality of mRNA translation into functional proteins. Specifically, MYC drives the translation of most protein ...
[77]
Progressive alterations in polysomal architecture and activation of ...
Jun 1, 2024 · Neuronal polysomal architecture undergoes progressive compaction in HD mice. Densely packed polysomes in HD are compatible with ribosome stalling phenomena.
[78]
Model-independent reorganization of translation in TDP-43 ... - bioRxiv
May 16, 2025 · Ribosome reorganization into larger polysomes is a common feature in ALS ... (b-c) Representative polysomal profiles and dot blot co-sedimentation ...
[79]
Increased cytoplasmic TDP-43 reduces global protein synthesis by ...
Next, polysome profile was obtained by adsorbance at 254 nm and free ribosomes and polyribosomes were collected in fractions. Immunoblotting experiments on ...
[80]
Global analysis of polysome-associated mRNA in vesicular ...
Jun 21, 2019 · Efficient protein synthesis by a viral mutant defective in mRNA cap methylation. (A) Phosphoimage analysis of an SDS-PAGE of proteins ...
[81]
Preferential Translation of Vesicular Stomatitis Virus mRNAs Is ... - NIH
These results show that EGFP mRNA expressed from the viral genome is translated much more efficiently than host-derived EGFP mRNA during VSV infection. Analysis ...
[82]
Reanalysis of ribosome profiling datasets reveals a function ... - Nature
Feb 2, 2023 · Our study presents the complete dual modes of RocA in blocking translation initiation and elongation, which underlie the potent antitumor effect of RocA.
[83]
Rocaglates as Antivirals: Comparing the Effects on Viral Resistance ...
Mar 3, 2022 · Rocaglates are potent broad-spectrum antiviral compounds with a promising safety profile. They inhibit viral protein synthesis for different RNA ...Missing: polysome | Show results with:polysome
[84]
Massively Parallel Polyribosome Profiling Reveals Translation ...
Sep 16, 2025 · Overall, our study provides insights into the molecular mechanisms of UTR mutations and their links to clinical impacts through translation ...<|control11|><|separator|>
[85]
Polysome-profiling in small tissue samples - PMC - PubMed Central
Oct 23, 2017 · Here we present a polysome-profiling technique applicable to large study designs, primary cells and frozen tissue samples such as those collected in biobanks.