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Codon Optimality Is a Major Determinant of mRNA Stability
Open accessAbstract
mRNA degradation represents a critical regulated step in gene expression. Although the major pathways in turnover have been identified, accounting for disparate half-lives has been elusive. We show that codon optimality is one feature that contributes greatly to mRNA stability. Genome-wide RNA decay analysis revealed that stable mRNAs are enriched in codons designated optimal, whereas unstable mRNAs contain predominately non-optimal codons. Substitution of optimal codons with synonymous, non-optimal codons results in dramatic mRNA destabilization, whereas the converse substitution significantly increases stability. Further, we demonstrate that codon optimality impacts ribosome translocation, connecting the processes of translation elongation and decay through codon optimality. Finally, we show that optimal codon content accounts for the similar stabilities observed in mRNAs encoding proteins with coordinated physiological function. This work demonstrates that codon optimization exists as a mechanism to finely tune levels of mRNAs and, ultimately, proteins.
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“These strategies have yielded modest improvements in RNA stability10, 13–16, and thus alternative approaches to RNA stabilization, such as circularization, are desirable.”
From Engineering circular RNA for potent and stable translation in eukaryotic cells (2018) · cites this paper as [15]
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“Furthermore, the rate of codon-dependent translation elongation has been a primary factor of mRNA stability, codon modification is critical for mRNA stability (Presnyak et al. 2015).”
From Modifications of mRNA vaccine structural elements for improving mRNA stability and translation efficiency (2022) · cites this paper as Presnyak et al. 2015
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“Furthermore, the rate of codon-dependent translation elongation has been a primary factor of mRNA stability, codon modification is critical for mRNA stability (Presnyak et al. 2015).”
From Modifications of mRNA vaccine structural elements for improving mRNA stability and translation efficiency (2022) · cites this paper as Presnyak et al. 2015
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“To improve the safety, efficacy, and stability of mRNA vaccines, researchers usually performed codon optimization172,239–243 on the antigen-coding sequence to enhance translation efficiency.”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [240]
In the citing paper
“Codon optimization in the mRNA sequence to e.g., match host transfer (t)RNA abundances, or as a determinant of introducing secondary structures, can drastically impact the protein synthesis rate and ribosome dwell time (i.e. mRNA functional half-life) [33,34]”
From The dawn of mRNA vaccines: the COVID-19 case (2021) · cites this paper as [33]
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Cites
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“Several ribosomal profiling studies have failed to detect codon-specific differences in the translation of optimal and non-optimal codons (Ingolia et al., 2009; Qian et al., 2012; Charneski and Hurst, 2013).”
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“The overall result is not surprising, as codon bias has been well studied (Gustafsson et al., 2004); however, the pattern of codon usage demonstrates that certain classes of mRNAs predominately use either optimal or non-optimal codons (Figures 3A and 3B; overrepresented codons in yellow,…”
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“Critically, optimal codons are postulated to be decoded faster and more accurately by the ribosome than non-optimal codons (Akashi, 1994; Drummond and Wilke, 2008), which are hypothesized to slow translation elongation (Novoa and Ribas de Pouplana, 2012; Tuller et al., 2010).”
BackgroundAn evolutionarily conserved mechanism for controlling the efficiency of protein translation
Tuller, T., Carmi, A., Vestsigian, K., Navon, S., Dorfan, Y., Zaborske, J., Pan, T., Dahan, O., Furman, I., & Pilpel, Y. (2010) · Cell · doi:10.1016/j.cell.2010.03.031 · Cited by 874 · cited 1×
“Critically, optimal codons are postulated to be decoded faster and more accurately by the ribosome than non-optimal codons (Akashi, 1994; Drummond and Wilke, 2008), which are hypothesized to slow translation elongation (Novoa and Ribas de Pouplana, 2012; Tuller et al., 2010).”
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Shaferman, M., Gencel, M., Alon, N., Alasad, K., Rotblat, B., Serohijos, A. W. R., Alfonta, L., & Bershtein, S. (2023) · Molecular Biology and Evolution · doi:10.1093/molbev/msad123 · Cited by 9
Base Composition, Codon Usage, and Patterns of Gene Sequence Evolution in Butterflies
Näsvall, K., Boman, J., Talla, V., & Backström, N. (2023) · Genome Biology and Evolution · doi:10.1093/gbe/evad150 · Cited by 12
Hammel, A., Neupert, J., & Bock, R. (2024) · Plant Molecular Biology · doi:10.1007/s11103-024-01415-2 · Cited by 11
“Overall, our findings are in agreement with studies in yeast and Chlamydomonas that also reported a strong influence of codon usage (and, presumably, translation rates) on mRNA stability (Barahimipour et al. 2015; Presnyak et al. 2015).”
ResultThe dynamics and functional impact of tRNA repertoires during early embryogenesis in zebrafish
Reimão-Pinto, M. M., Behrens, A., Forcelloni, S., Fröhlich, K., Shunji, K. A. Y. A., & Nedialkova, D. D. (2024) · The EMBO Journal · doi:10.1038/s44318-024-00265-4 · Cited by 11
“To address these questions, we used the codon stabilization coef fi cient (CSC), a metric that represents the Pearson correlation coef fi cient between the occurrence of each codon in individual mRNA transcripts and their half-life (Presnyak et al, 2015).”
Torkzaban, B., Zhu, Y., Lopez, C., Alexander, J., Ma, J., Sun, Y., Maschhoff, K. R., Hu, W., Jacob, M. H., Lin, D., et al. (2025) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2025.102453 · Cited by 11
Self-citationWei, Z., Zhang, S., Wang, X., Xue, Y., Dang, S., & Zhai, J. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1524317 · Cited by 16
“The selection of codons within this region directly affects mRNA stability and translation ef fi ciency (80, 81).”
DrosophilaX-Linked Genes Have Lower Translation Rates than Autosomal Genes
Zhang, Z., & Presgraves, D. C. (2015) · Molecular Biology and Evolution · doi:10.1093/molbev/msv227 · Cited by 10
McCamphill, P. K., Ferguson, L., & Sossin, W. S. (2017) · Journal of Neurochemistry · doi:10.1111/jnc.14030 · Cited by 11
“One possibility is the level of rare codons in the open-reading frame of a message that causes elongation to become rate limiting, and leads to degradation of the mRNA through quality control pathways (Presnyak et al. 2015).”
BackgroundBansal, S., Mallikarjuna, M. G., Balamurugan, A., Nayaka, S. C., & Prakash, G. (2022) · Journal of Fungi · doi:10.3390/jof8111134 · Cited by 9
Li, B., Zeis, P., Zhang, Y., Alekseenko, A., Fürst, E., Sanchez, Y. P., Lin, G., Tekkedil, M. M., Piazza, I., Steinmetz, L. M., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36586-x · Cited by 11
Gurjar, P., Karuvantevida, N. S., Rzhepakovsky, I. V., Khan, A. A., & Khandia, R. (2023) · Vaccines · doi:10.3390/vaccines11020487 · Cited by 11
“In unstable RNAs, more than 60% of the codons are non-optimal [54].”
BackgroundSystems to study codon effect on post-transcriptional regulation of gene expression
Wu, Q., & Bazzini, A. (2017) · Methods · doi:10.1016/j.ymeth.2017.11.006 · Cited by 11
Waardenburg Syndrome Expression and Penetrance
Shelby, M. (2017) · Journal of Rare Diseases Research & Treatment · doi:10.29245/2572-9411/2017/6.1118 · Cited by 11
Barros, G. C., Requião, R. D., Carneiro, R. L., Masuda, C. A., Moreira, M. H., Rossetto, S., Domitrovic, T., & Palhano, F. L. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100586 · Cited by 11
“Based on Pearson’s correlation between the frequency of occurrence of each codon in each mRNA and the mRNA half-lives, Coller and colleagues created the codon occurrence to mRNA stability coefficient (CSC) [42].”
MethodInfluentialWang, J., Lin, Y., & Xi, M. (2021) · Genes · doi:10.3390/genes12101467 · Cited by 11
“Codon usage bias influences transcription [12,13], protein translation [14,15] and gene expression levels [16,17].”
BackgroundVillada, J. C., Brustolini, O. J. B., & da Silveira, W. B. (2017) · DNA Research · doi:10.1093/dnares/dsx014 · Cited by 11
Transcriptome Analysis of Core Dinoflagellates Reveals a Universal Bias towards “GC” Rich Codons
Williams, E., Place, A. R., & Bachvaroff, T. R. (2017) · Marine Drugs · doi:10.3390/md15050125 · Cited by 12
“A lack of transcripts that are differentially biased in their use of infrequent codons is in agreement with both the observation of long RNA half lives in dinoflagellates [15] and the observation that RNA turnover is much more rapid in RNAs with non-optimal codons [32].”
BackgroundStrong selection at the level of codon usage bias: evidence against the Li-Bulmer modelPreprint
Machado, H. E., Lawrie, D. S., & Petrov, D. A. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/106476 · Cited by 11
“In addition to speed and accuracy, there is evidence that other processes are affected by codon composition, such as cotranslational folding (Pechmann & Frydman 2013), RNA stability (Presnyak et al. 2015), and transcription (Carlini & Stephan 2003; Newman et al. 2016; Zhou et al. 2016).”
BackgroundInfluentialNoise control is a primary function of microRNAs and post-transcriptional regulationPreprint
Schmiedel, J. M., Marks, D. S., Lehner, B., & Blüthgen, N. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/168641 · Cited by 10
“…collected quantitative transcriptomes and proteomes for E. coli (Taniguchi et al., 2010), S. cerevisiae (Kulak et al., 2014; Lawless et al., 2016; Presnyak et al., 2015), Capsaspora owczarzaki (Sebé-Pedrós et al., 2013; Sebé-Pedrós et al., 2016b), mouse (Geiger et al., 2013; Jovanovic et al.,…”
BackgroundMethodLinking the dynamics of chromatin occupancy and transcription with predictive modelsPreprint
Tran, T. Q., MacAlpine, H. K., Tripuraneni, V., Mitra, S., MacAlpine, D. M., & Hartemink, A. J. (2021) · Genome Research · doi:10.1101/gr.267237.120 · Cited by 11
Mercier, B. C., Labaronne, E., Cluet, D., Guiguettaz, L., Fontrodona, N., Bicknell, A. A., Corbin, A., Wencker, M., Aubé, F., Modolo, L., et al. (2024) · Genome Research · doi:10.1101/gr.277863.123 · Cited by 11
“Consistent with the random forest analysis, in resting T cells, we could clearly see a nucleotide bias within codons bearing positive or negative TDD-CSC and TID-CSCs (Fig.”
BackgroundMethodInfluentialCubar: a versatile package for codon usage bias analysis in R
Liu, M., Zi, B., Zhang, H., & Zhang, H. (2025) · Genetics · doi:10.1093/genetics/iyaf191 · Cited by 10
The mRNA-Based Innovative Strategy: Progress and Challenges
Zhou, H., Wei, D., Chen, Z., Chen, H., Dong, C., Cai, W., Wang, J., Liu, X., Li, Y., Yang, Y., et al. (2026) · Nano-Micro Letters · doi:10.1007/s40820-025-01906-x · Cited by 17
“As the coding region of mRNA, the optimization of codons in the ORF is closely related to protein yield [65, 66].”
Sharma, A. K., Venezian, J., Shiber, A., Kramer, G., Bukau, B., & O’Brien, E. P. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2026362118 · Cited by 10
Katopodi, T., Petanidis, S., Grigoriadou, E., Anestakis, D., Charalampidis, C., Chatziprodromidou, I. P., Floros, G., Eskitzis, P., Zarogoulidis, P., Koulouris, C., et al. (2024) · Pharmaceutics · doi:10.3390/pharmaceutics16040455 · Cited by 11
“…self-amplifying RNAs, which encode both the antigen and the viral replication machinery that allows for intracellular RNA amplification and abundant protein production, conventional mRNA-based vaccines only encode the antigen of interest and contain 5 ′ and 3 ′ untranslated regions (UTRs) [10].”
BackgroundThe dawn of a new Era: mRNA vaccines in colorectal cancer immunotherapy
Song, J., Zhang, Y., Zhou, C., Zhan, J., Cheng, X., Huang, H., Mao, S., & Zong, Z. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.112037 · Cited by 10
Orb2 enables rare-codon-enriched mRNA expression during Drosophila neuron differentiation
Stewart, R. K., Nguyen, P., Laederach, A., Volkan, P., Sawyer, J. K., & Fox, D. T. (2024) · Nature Communications · doi:10.1038/s41467-024-48344-8 · Cited by 8
Baeza, M., Sepúlveda, D., Cifuentes, V., & Alcaı́no, J. (2024) · Frontiers in Microbiology · doi:10.3389/fmicb.2024.1414422 · Cited by 10
“…tend to have a higher content of preferred codons (above 85% on average) and unstable mRNAs, such as those encoding polypeptides involved in yeast pheromone response and mitochondrial ribosomal proteins, have a lower content of preferred codons (an average of about 45%; Presnyak et al., 2015).”
BackgroundTranslation elongation inhibitors stabilize select short-lived transcripts
Rosa-Mercado, N. A., Buskirk, A. R., & Green, R. (2024) · RNA · doi:10.1261/rna.080138.124 · Cited by 10
RNA degradation triggered by decapping is largely independent of initial deadenylation
Audebert, L., Feuerbach, F., Zedan, M., Schürch, A. P., Decourty, L., Namane, A., Permal, E., Weis, K., Badis, G., & Saveanu, C. (2024) · The EMBO Journal · doi:10.1038/s44318-024-00250-x · Cited by 11
“While codon usage, ribosome occupancy and stalling have been shown to affect mRNA half-life in a wide range of species, from yeast (Presnyak et al, 2015; Chan et al, 2018) to zebra fi sh (Mishima and Tomari, 2016) and mammals (Wu et al, 2019), the mechanisms by which ribosomal activity is linked to…”
InfluentialFurther Evidence for Strong Nonneutrality of Yeast Synonymous Mutations
Shen, X., Song, S., Li, C., & Zhang, J. (2024) · Molecular Biology and Evolution · doi:10.1093/molbev/msae224 · Cited by 9
“…can affect a wide variety of molecular processes such as pre-mRNA splicing (Chamary et al. 2006), mRNA folding (Park et al. 2013) and stability (Presnyak et al. 2015; Chen et al. 2017), translational initiation (Kudla et al. 2009), efficiency (Qian et al. 2012b; Frumkin et al. 2018), and…”
Ishibashi, K., Shichino, Y., Han, P., Wakabayashi, K., Mito, M., Inada, T., Kimura, S., Iwasaki, S., & Mishima, Y. (2024) · PLoS Biology · doi:10.1371/journal.pbio.3002887 · Cited by 11
Circular RNA Telomerase Reverses Endothelial Senescence in Progeria
Qin, W., Castillo, K., Li, H., Nguyen, T. K. C., Kiss, D., Cooke, J. P., & Mojiri, A. (2025) · Aging Cell · doi:10.1111/acel.70021 · Cited by 10
“We employed a TERT circRNA with optimal codon sequences to increase both protein output and RNA lifespan (Hanson and Coller 2018; Presnyak et al. 2015).”
The Bright Future of mRNA as a Therapeutic Molecule
Vélez, D. E., Torres, B. L., & Hernández, G. (2025) · Genes · doi:10.3390/genes16040376 · Cited by 11
Berlanga, J. J., Matamoros, T., Rodríguez‐Pulido, M., Sáiz, M., Bayón, M. N., Toribio, R., & Ventoso, I. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkaf261 · Cited by 11
“…for its role in regulating mRNA stability and protein quality control, but it can also influence translation initiation by a yet unknown mechanism [ 16–19 ]. mRNAs with a synonymous codon composition adapted to aa-transfer RNA (tRNA) availability in a given cell type or organism tend to be more…”
Codon Usage Bias in Human RNA Viruses and Its Impact on Viral Translation, Fitness, and Evolution
Ventoso, I. (2025) · Viruses · doi:10.3390/v17091218 · Cited by 11
“Thus, codon usage, translation, and mRNA stability are closely linked through pathways that sense and connect ribosomal flux with the main mRNA degradation activities of the cell [9,10].”
RNA deadenylation complexes in development and diseases
Liu, Y., Ramkumar, N., & Vu, L. (2023) · Biochemistry and Cell Biology · doi:10.1139/bcb-2022-0325 · Cited by 10
Pu, F., Wang, R., Yang, X., Hu, X., Wang, J., Zhang, L., Zhao, Y., Zhang, D., Liu, Z., & Liu, J. (2023) · Journal of Basic Microbiology · doi:10.1002/jobm.202200624 · Cited by 10
“This biased synonymous codon usage is not neutral but involved in nucleotide usage bias [25, 26], mRNA stability [27, 28], translation accuracy, efficiency [29, 30], and protein folding formation [31].”
BackgroundRahaman, S., Faravelli, S., Voegeli, S., & Becskei, A. (2023) · Science Advances · doi:10.1126/sciadv.adh9545 · Cited by 11
“The efficient decoding permits fast translational elongation, which at the same time stabilizes mRNAs and consequently, mRNAs enriched in optimal codons have typically longer half-lives ( 2 , 3 ).”
Heterologous Biosynthesis of the Fungal Sesquiterpene Trichodermol in Saccharomyces cerevisiae
Liu, J., Zhai, Y., Zhang, Y., Zhu, S., Liu, G., & Che, Y. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.01773 · Cited by 10
OTTER, a new method for quantifying absolute amounts of tRNAs
Nagai, A., Mori, K., Shiomi, Y., & Yoshihisa, T. (2021) · RNA · doi:10.1261/rna.076489.120 · Cited by 12
“…analyses, especially those via ribosome profiling (Ingolia et al. 2009), have revealed a global view that codon selection affects both the efficiency (Shah and Gilchrist 2011; Qian et al. 2012; Goodarzi et al. 2016) and accuracy (Drummond and Wilke 2008; Krisko et al. 2014) of translation.”
BackgroundA unifying network modeling approach for codon optimization
Karaşan, O. E., Şen, A., Tiryaki, B., & Çiçek, A. E. (2022) · Bioinformatics · doi:10.1093/bioinformatics/btac428 · Cited by 10
Attenuation of Viruses by Large-Scale Recoding of their Genomes: the Selection Is Always Biased
Osterrieder, N., & Kunec, D. (2018) · Current Clinical Microbiology Reports · doi:10.1007/s40588-018-0080-3 · Cited by 11
“Codon choice affects translation efficiency [28] , protein folding [29] , and mRNA stability [30] , but the significance of codon bias despite of decades of investigation remains unclear.”
BackgroundGenome‐scale molecular principles of mRNA half‐life regulation in yeast
Basu, S., Mallik, S., Hait, S., & Kundu, S. (2020) · FEBS Journal · doi:10.1111/febs.15670 · Cited by 9
Arabidopsis uORF-containing mRNAs behave differently from NMD targetsPreprint
Wu, H.-Y. L., & Hsu, P. Y. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.09.16.460672 · Cited by 9
Kanai, Y., Onishi, M., Yoshida, Y., Kotaki, T., Minami, S., Nouda, R., Yamasaki, M., Enoki, Y., & Kobayashi, T. (2023) · Journal of Virology · doi:10.1128/jvi.00492-23 · Cited by 9
Sotelo-Ramírez, C. E., Camarena, B., Sanabrais‐Jiménez, M. A., Zaragoza-Hoyos, J. U., Ordoñez-Martínez, B., Escamilla-Orozco, R. I., & Gómez‐González, B. (2023) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s420952 · Cited by 9
“15 Studies have found that mRNA stability is affected by the number of optimal and non-optimal codons; 33,34 TLR2 and TLR6 variants could thus be related to RNA stability conferring a protective effect from schizophrenia.”
BackgroundCzarnocka-Cieciura, A., Poznański, J. T., Turtola, M., Tomecki, R., Krawczyk, P. S., Mroczek, S., Orzeł, W., Saha, U., Jensen, T. H., Dziembowski, A., et al. (2024) · The EMBO Journal · doi:10.1038/s44318-024-00258-3 · Cited by 9
“Previous studies have estimated bulk yeast mRNA half-lives of 12 min or even lower (Miller et al, 2011; Sun et al, 2012; Neymotin et al, 2014; Presnyak et al, 2015; Chan et al, 2018).”
InfluentialRibosomes modulate transcriptome abundance via generalized frameshift and out-of-frame mRNA decay
Zhang, Y., Nersisyan, L., Fürst, E., Alexopoulos, I., Santolaria, C., Huch, S., Bassot, C., Garré, E., Sunnerhagen, P., Piazza, I., et al. (2025) · Molecular Cell · doi:10.1016/j.molcel.2025.04.022 · Cited by 11
mRNA Stability: An Unresolved Challenge for Broad Therapeutic Applications
Wang, Y., Wang, X., & Lu, Y. (2025) · Biotechnology Journal · doi:10.1002/biot.70146 · Cited by 11
“Specifically, the median half-life of mRNAs with fewer than 40% of the best codons was 5.3 min, while those with more than 70% of the best codons had a median half-life of 20.1 min [24].”
InfluentialCaulier, G., Siblini, J., Sene, L., Mauxion, F., & Séraphin, B. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkaf1401 · Cited by 12
“Altogether, these observations provide a molecular mechanism to explain how codon usage modulates mRNA stability, a feature observed in several organisms, including yeast and humans [ 179 –181 ].”
Ikrar, T., Muchsin, W., & Sophian, A. (2026) · Journal of Controlled Release · doi:10.1016/j.jconrel.2026.115019 · Cited by 10
Codon codes: Codon usage bias influences many levels of gene expression
Dang, Y., Dong, Y., & GuiPing, R. E. N. (2019) · Scientia Sinica Vitae · doi:10.1360/ssv-2019-0103 · Cited by 9
“为了解 开这个谜题 , Presnyak 等人 [72] 把每一个密码子对于 .”
Wang, H. H., Wang, M., Feng, X., Li, Y., Zhang, D., Cheng, Y., Liu, J., Wang, X., Zhang, L., La, H., et al. (2022) · Frontiers in Veterinary Science · doi:10.3389/fvets.2022.984962 · Cited by 9
Co-Translational Quality Control Induced by Translational Arrest
Matsuo, Y., & Inada, T. (2023) · Biomolecules · doi:10.3390/biom13020317 · Cited by 10
Sejour, R., Leatherwood, J., Yurovsky, A., & Futcher, B. (2023) · eLife · doi:10.7554/elife.89656 · Cited by 12
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Codon Bias Can Determine Sorting of a Potassium Channel Protein
Kithil, M., Engel, A. J., Langhans, M., Rauh, O., Cartolano, M., Etten, J. L. V., Moroni, A., & Thiel, G. (2021) · Cells · doi:10.3390/cells10051128 · Cited by 8
“There is increasing experimental evidence for a much more complex role of codon choice in that synonymous codons, for example, can alter mRNA splicing as well as mRNA folding and stability [6,7].”
BackgroundDaron, J., & Bravo, I. G. (2021) · Viruses · doi:10.3390/v13091800 · Cited by 9
Li, Y., Wang, R., Wang, H. H., Pu, F., Feng, X., Jin, L. H., Ma, Z., & Ma, X. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.771010 · Cited by 9
Li, Q., Vetter, L., Veith, Y., Christ, E., Végvári, Á., Sahin, C., Ribacke, U., Wahlgren, M., Ankarklev, J., Larsson, O., et al. (2024) · iScience · doi:10.1016/j.isci.2024.111167 · Cited by 9
“36,50 This enables a systemic modulation of protein synthesis during the translation elongation step.”
mRNA vaccine-a desirable therapeutic strategy for surmounting COVID-19 pandemic
Chen, P., Shi, X., He, W., Zhong, G., Tang, Y., Wang, H., & Zhang, P. (2022) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2022.2040330 · Cited by 10
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“Optimal and unbiased codons are used in mRNA to be robustly translated [44].”
BackgroundOptimization of ribosome utilization in Saccharomyces cerevisiae.
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The ribosome quality control factor Asc1 determines the fate of HSP70 mRNA on and off the ribosome
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Integrated tRNA, transcript, and protein profiles in response to steroid hormone signaling
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“…supply to translating ribosomes, the concentration for each tRNA isoacceptor would become equal when tRNA abundance is balanced with codon usage (Qian et al. 2012), providing a possible explanation for the uniformity in ribosome occupancy while accounting for the importance of tRNA abundance in…”
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Plant mRNA decay: extended roles and potential determinants
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Different Plant Species Have Common Sequence Features Related to mRNA Degradation Intermediates
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Decoupled degradation and translation enables noise modulation by poly(A) tails
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“Various strategies exist to improve protein expression, including codon optimization [26,27], the substitution of rare codons, increasing GC content [28], and optimizing secondary structures [12,13].”
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“Currently, the optimization of CDS has been extensively investigated, encompassing methods based on codon optimality theory 6 as well as those based on deep learning.”
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“Previous studies have demonstrated that codon usage bias is a major determinant of mRNA stability, 57 and the introduction of rare codons results in mRNA destabi-lisation.”
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“Codon-specific translation rates, and therefore codon optimality, are generally determined by averaging ribosome occupancy of all instances of a codon across the transcriptome [ 8–10 , 88–90 ].”
De novo design of synthetic microbial genomes
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“Genetic redundancy can also be used to regulate the GC-content of the genome or to control the secondary structure of mRNA, which in turn influences translation (initiation) rates and stability of mRNA 68,71,72 .”
Human DHX29 detects nonoptimal codon usage to regulate mRNA stability
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“Each facet of the mRNA payload has been the focus of optimization efforts (for example, capping 34,35,237 , codon optimization 46,238 , chemical”
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“Whereas, a recent focus in the fi eld has been the correlation between codon optimality, translation elongation, and mRNA stability (76, 77).”
Engineering circular RNA for molecular and metabolic reprogramming
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“Hence, there is a need to develop a new approach including circularization to enhance RNA stability (Holtkamp et al. 2006; Kaczmarek et al. 2017; Kariko et al. 2011; Kuhn et al. 2010; Presnyak et al. 2015).”
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“…of SRP-mediated downregulation of mRNA levelsduringheatshock,itisplausiblethattheSRP-driveninhibitionof translation may lead to degradation of the underlying mRNA as suggested by multiple studies that investigated mechanisms whereby translation rates directly impact on half-life of mRNA 71 – 73 .”
Unlock the sustained therapeutic efficacy of mRNA
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“Coller’s [72] and other laboratories [63] by showing that in S.”
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The Dynamic Codon Biaser: calculating prokaryotic codon usage biases
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“The use of synonymous codons is also influenced by multiple factors, such as genome size, gene length, gene expression level, protein secondary structure, and gene density [28,29].”
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“There 56 are many forces acting on codon bias – including mutational biases and selection for 57 mRNA stability [35] – but the codon usage patterns of genes are also thought to be 58 optimized to the relative abundance of tRNAs within the cell to facilitate rapid 59 translation.”
BackgroundThe regulatory landscape of interacting RNA and protein pools in cellular homeostasis and cancer
Gallardo-Dodd, C. J., & Kutter, C. (2024) · Human Genomics · doi:10.1186/s40246-024-00678-6 · Cited by 9
“The balance of codons and anticodons is further known to mediate translation elongation rates and mRNA stability [134].”
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Harnessing Computational Strategies to Overcome Challenges in mRNA Vaccines
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Viral RNA blocks circularization to evade host codon usage control
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“Although codon usage has previously been shown to affect initiation 7–9 , its relative contribution compared with other effects was unclear 38,49 .”
A comparative study of the COVID-19 vaccine efficacy among cancer patients: mRNA versus non-mRNA
Rachman, A., Iriani, A., Sukrisman, L., Rajabto, W., Mulansari, N. A., Lubis, A. M., Cahyanur, R., Prasetyawaty, F., Priantono, D., Rumondor, B. B., et al. (2023) · PLoS ONE · doi:10.1371/journal.pone.0281907 · Cited by 8
“is critical for mRNA stability because the rate of codon-dependent translation elongation has been identified as a primary factor of mRNA stability [23, 30].”
BackgroundIdentification and in silico characterization of CSRP3 synonymous variants in dilated cardiomyopathy
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Metadata
- Authors
- Presnyak, V., Alhusaini, N., Chen, Y.-H., Martin, S., Morris, N., Kline, N., Olson, S., Weinberg, D., Baker, K. E., Graveley, B. R., & Coller, J.
- Affiliations
- Case Western Reserve University (US)
- UConn Health (US)
- University of California, San Francisco (US)
- Corresponding author
- Coller, Jeff
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2015-03
- Volume
- 160
- Issue
- 6
- Pages
- 1111-1124
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4359748
- OpenAlex
- W2013321787
- Cited by
- 1,078
- References
- 43
- Citations by year
- 2026: 94 · 2025: 139 · 2024: 122 · 2023: 115 · 2022: 77 · 2021: 127 · 2020: 93 · 2019: 70 · 2018: 96 · 2017: 68 · 2016: 57 · 2015: 20
- FWCI
- 34.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (GM080465, GM095621)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Keywords
- codon optimality, mRNA stability, mRNA degradation, codon usage bias, synonymous codons, ribosome translocation, translation elongation, gene expression regulation, mRNA half-life
- MeSH terms
- Codon, RNA, Fungal, RNA, Messenger, Saccharomyces cerevisiae, Protein Biosynthesis, RNA Stability
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