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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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In the citing paper
“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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Citations
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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Items 301–400 of 998
RNA degradation is required for the germ-cell to maternal transition in Drosophila
Blatt, P., Wong-Deyrup, S. W., McCarthy, A., Breznak, S. M., Hurton, M. D., Upadhyay, M., Bennink, B., Camacho, J., Lee, M. T., & Rangan, P. (2021) · Current Biology · doi:10.1016/j.cub.2021.04.052 · Cited by 33
Gillen, S. L., Giacomelli, C., Hodge, K., Zanivan, S. R., Bushell, M., & Wilczynska, A. (2021) · Genome biology · doi:10.1186/s13059-021-02494-w · Cited by 34
Decoding the effects of synonymous variants
Zeng, Z., Aptekmann, A. A., & Bromberg, Y. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab1159 · Cited by 33
Extensive allele‐specific translational regulation in hybrid mice
Hou, J., Wang, X., McShane, E., Zauber, H., Sun, W., Selbach, M., & Chen, W. (2015) · Molecular Systems Biology · doi:10.15252/msb.156240 · Cited by 33
“It might not change mRNA – ribosome association and thus not susceptible to our ADTE measurement based on polysome profiling (Tuller et al , 2010; Novoa & Ribas de Pouplana, 2012; Presnyak et al , 2015).”
High-throughput 5′P sequencing enables the study of degradation-associated ribosome stalls
Zhang, Y., & Pelechano, V. (2021) · Cell Reports Methods · doi:10.1016/j.crmeth.2021.100001 · Cited by 32
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BackgroundMethodInfluentialA nascent peptide code for translational control of mRNA stability in human cells
Burke, P. C., Park, H., & Subramaniam, A. R. (2022) · Nature Communications · doi:10.1038/s41467-022-34664-0 · Cited by 31
Varier, R. A., Sideri, T. C., Capitanchik, C., Manova, Z., Calvani, E., Rossi, A., Edupuganti, R. R., Ensinck, I., Chan, V. W., Patel, H., et al. (2022) · eLife · doi:10.7554/elife.84034 · Cited by 27
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Forbes-Beadle, L., Love, J., Shapovalova, Y., Artemev, A., Rattray, M., & Ashe, H. L. (2023) · PLoS Biology · doi:10.1371/journal.pbio.3001956 · Cited by 24
“The CSC value was calculated for each codon as previously described [43,84].”
MethodAre Nonsynonymous Transversions Generally More Deleterious than Nonsynonymous Transitions?
Zou, Z., & Zhang, J. (2020) · Molecular Biology and Evolution · doi:10.1093/molbev/msaa200 · Cited by 32
Mutation bias within oncogene families is related to proliferation-specific codon usage
Benisty, H., Weber, M. L., Hernandez‐Alias, X., Schaefer, M. H., & Serrano, L. G. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2016119117 · Cited by 30
“cerevisiae (35) and Escherichia coli (36).”
mRNA-Enhanced Cell Therapy and Cardiovascular Regeneration
Chanda, P. K., Sukhovershin, R. A., & Cooke, J. P. (2021) · Cells · doi:10.3390/cells10010187 · Cited by 30
“Furthermore, the mRNA sequence can be modified to include synonymous codons that are optimal for a specific cell type (reflecting tRNA abundance), or a “translational ramp” (specific initial amino acid sequence that enhances translation) [14,15].”
BackgroundA Code Within a Code: How Codons Fine-Tune Protein Folding in the Cell
Komar, A. A. (2021) · Biochemistry (Moscow) · doi:10.1134/s0006297921080083 · Cited by 30
Plastomes of Bletilla (Orchidaceae) and Phylogenetic Implications
Han, S., Wang, R., Hong, X., Wu, C., Zhang, S., & Kan, X. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231710151 · Cited by 30
Co-translational binding of importins to nascent proteins
Seidel, M., Romanov, N., Obarska-Kosińska, A., Becker, A., de Azevedo, N. T. D., Provaznik, J., Nagaraja, S. R., Landry, J. J. M., Beneš, V., & Beck, M. (2023) · Nature Communications · doi:10.1038/s41467-023-39150-9 · Cited by 27
“enriched at the observed onsets of many cargoes, are not only a hallmark of the NLS motif but they are 312 also associated with less abundant tRNAs (49) and thus likely reduce translation speed to warrant 313”
BackgroundTranslation Regulation in Skin Cancer from a tRNA Point of View
Grafanaki, K., Anastasakis, D. G., Kyriakopoulos, G. C., Skeparnias, I., Georgiou, S., & Stathopoulos, C. (2018) · Epigenomics · doi:10.2217/epi-2018-0176 · Cited by 31
“Advances in ribosome profiling made evident that codon bias serves as an auxiliary code that ensures the efficiency and fidelity of translation and, under various conditions, affects mRNA stability and shapes the proteome, allowing swift translation reprogramming to maintain homeostasis [40,247].”
BackgroundOptimizing assembly and production of native bispecific antibodies by codon de-optimization
Magistrelli, G., Poitevin, Y., Schlosser, F., Pontini, G., Malinge, P., Josserand, S., Corbier, M., & Fischer, N. (2017) · mAbs · doi:10.1080/19420862.2016.1267088 · Cited by 28
“ing at maximizing translation and stability of mRNA (mRNA).(18-20) A variety of software are available for synthetic gene design, as well as computational procedures to evaluate the effect of codon optimization.”
MethodRobust genome and cell engineering via in vitro and in situ circularized RNAs
Tong, M., Palmer, N. D., Dailamy, A., Kumar, A., Khaliq, H., Han, S., Finburgh, E. N., Wing, M. K., Hong, C., Xiang, Y., et al. (2024) · Nature Biomedical Engineering · doi:10.1038/s41551-024-01245-z · Cited by 32
“Correspondingly, we synthesized peptides for epitopes 2, 7, 8, 9, 12, 15 and 16 as our predictions suggested that these epitopes would induce a reduction in immune response for the HLA-A*0201 allele (Supplementary Fig.”
Analysis of codon usage patterns in Morus notabilis based on genome and transcriptome data
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“Codon usage has been identified as a major determinant of mRNA stability (Presnyak et al., 2015).”
BackgroundPhienluphon, A., Mhuantong, W., Boonyapakron, K., Deenarn, P., Champreda, V., Wichadakul, D., & Suwannarangsee, S. (2019) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-019-09667-5 · Cited by 29
“Moreover, the variation in relative transcription levels of different BGL-CTS fusion proteins found in this study may be due to different codon optimality among fusion proteins that can affect the levels of mRNA (Presnyak et al. 2015; Zhou et al. 2016).”
BackgroundBoussaid, I., Goff, S. L., Floquet, C., Gautier, E., Raimbault, A., Viailly, P., Dulaimi, D. A., Burroni, B., Dusanter‐Fourt, I., Hatin, I., et al. (2020) · Haematologica · doi:10.3324/haematol.2019.239970 · Cited by 30
Splicing-accessible coding 3′UTRs control protein stability and interaction networks
Preußner, M., Gao, Q., Morrison, E., Herdt, O., Finkernagel, F., Schümann, M., Krause, E., Freund, C., Chen, W., & Heyd, F. (2020) · Genome biology · doi:10.1186/s13059-020-02102-3 · Cited by 29
Control of Multigene Expression Stoichiometry in Mammalian Cells Using Synthetic Promoters
Patel, Y. D., Brown, A. J., Zhu, J., Rosignoli, G., Gibson, S. J., Hatton, D., & James, D. C. (2021) · ACS Synthetic Biology · doi:10.1021/acssynbio.0c00643 · Cited by 29
A (dis)integrated stress response: Genetic diseases of eIF2α regulators
English, A. M., Green, K. M., & Moon, S. L. (2021) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1689 · Cited by 33
“, 2013), its rate of translation (as reduced translation is associated with more rapid decay; Presnyak et al., 2015), RNA modifications (reviewed in Boo & Kim, 2020), specific RNA motifs, and cellular conditions such as cellular stress, as will be discussed below.”
BackgroundAtlas of mRNA translation and decay for bacteria
Huch, S., Nersisyan, L., Ropat, M., Barrett, D., Wu, M., Wang, J., Valeriano, V. D., Vardazaryan, N., Huerta‐Cepas, J., Wu, W., et al. (2023) · Nature Microbiology · doi:10.1038/s41564-023-01393-z · Cited by 28
“7a); (2) simplicity, without the need for subcellular fractionation(40); (3) being applicable to stored RNA samples(5,41); and (4) providing information about in vivo ribosome position, codon-specific ribosome stalls and amino acid limitations in species containing RNase J, which is estimated to represent ∼60% of bact…”
BackgroundConsiderations in the Use of Codon Optimization for Recombinant Protein Expression
Mauro, V. P., & Chappell, S. A. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-8730-6_18 · Cited by 29
Gao, W. N. D., Gallardo-Dodd, C. J., & Kutter, C. (2021) · Genome Research · doi:10.1101/gr.275944.121 · Cited by 30
“Additionally, codon optimality has been shown to be a major determinant of mRNA stability (Presnyak et al. 2015).”
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“Recent studies have implicated codon optimality as an important determinant 705 of mRNA stability in eukaryotes [85–88] and it is conceivable that PUM proteins could be directly 706 mediating some of these effects.”
BackgroundThe ribosome as a platform to coordinate mRNA decay
Müller, M. B. D., Becker, T. A., Denk, T., Hashimoto, S., Inada, T., & Beckmann, R. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkaf049 · Cited by 31
“However, significant differences exist in the availability of individual tRNAs and their charging status which influence ribosomal elongation rates along mRNAs [ 2 , 50 ] and are also affected by transfer RNA (tRNA) isoaccep-tors and wobble base pairing [ 51 ].”
Whisper mutations: cryptic messages within the genetic code
Fåhræus, R., Marı́n, M., & Olivares‐Illana, V. (2015) · Oncogene · doi:10.1038/onc.2015.454 · Cited by 28
A Universal Code for mRNA Stability?
Chen, Y.-H., & Coller, J. M. (2016) · Trends in Genetics · doi:10.1016/j.tig.2016.08.007 · Cited by 28
Self-citationStable G-quadruplex enabling sequences are selected against by the context-dependent codon bias
Arachchilage, G. M., Arachchilage, M. H., Venkataraman, A., Piontkivska, H., & Basu, S. (2019) · Gene · doi:10.1016/j.gene.2019.02.006 · Cited by 27
Isogai, S., Okahashi, N., Asama, R., Nakamura, T., Hasunuma, T., Matsuda, F., Ishii, J., & Kondo, A. (2021) · Metabolic Engineering Communications · doi:10.1016/j.mec.2021.e00169 · Cited by 28
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Distinct responses to rare codons in select Drosophila tissues
Allen, S. R., Stewart, R. K., Rogers, M., Ruiz, I. J., Cohen, E., Laederach, A., Counter, C. M., Sawyer, J. K., & Fox, D. T. (2022) · eLife · doi:10.7554/elife.76893 · Cited by 30
“…et al., 2021; Z. Zhou et al., 2016) or can negatively impact mRNA stability through a growing number of characterized mechanisms and in numerous model systems (Bazzini et al., 2016; Burow et al., 2018; Buschauer et al., 2020; Presnyak et al., 2015; Radhakrishnan et al., 2016; Wu et al., 2019).”
BackgroundDeveloping mRNA Nanomedicines with Advanced Targeting Functions
Wang, J., Cai, L., Li, N., Luo, Z., Ren, H., Zhang, B., & Zhao, Y. (2025) · Nano-Micro Letters · doi:10.1007/s40820-025-01665-9 · Cited by 33
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“68,69 A primary strategy for optimizing the CDS is codon optimization, which involves replacing rare codons with synonymous, more-frequently used codons in the host organism.”
The Impact of Selection at the Amino Acid Level on the Usage of Synonymous Codons
Błażej, P., Mackiewicz, D., Wnętrzak, M., & Mackiewicz, P. (2017) · G3 Genes Genomes Genetics · doi:10.1534/g3.116.038125 · Cited by 28
“Although translational selection is thought to be the dominant explanation of systematic variation in codon usage among genes (Chaney and Clark 2015; Plotkin and Kudla 2011; Quax et al. 2015), several other factors related to codon bias have been put forward.”
The ribosome collision sensor Hel2 functions as preventive quality control in the secretory pathway
Matsuo, Y., & Inada, T. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.108877 · Cited by 27
Mechanisms and Delivery of tRNA Therapeutics
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Roles of the CCR4‐Not complex in translation and dynamics of co‐translation events
Collart, M. A., Audebert, L., & Bushell, M. (2023) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1827 · Cited by 26
“…using transcription shut-off and an rpb1-1 mutant (Presnyak et al., 2015) or reporter constructs with different contents in optimal codons transcribed from a GAL promoter and transferring cells growing in galactose to glucose to follow mRNA decay (Buschauer et al., 2020; Presnyak et al., 2015).”
BackgroundMethodResultInfluentialThe Molecular Mechanisms Underlying Hidden Phenotypic Variation among Metallo-β-Lactamases
Socha, R. D., Chen, J. Z., & Tokuriki, N. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.01.041 · Cited by 28
The fitness landscape of the codon space across environments
Fragata, I., Matuszewski, S., Schmitz, M. A., Bataillon, T. M., Jensen, J. D., & Bank, C. (2018) · Heredity · doi:10.1038/s41437-018-0125-7 · Cited by 26
Signatures of optimal codon usage in metabolic genes inform budding yeast ecology
LaBella, A. L., Opulente, D. A., Steenwyk, J. L., Hittinger, C. T., & Rokas, A. (2021) · PLoS Biology · doi:10.1371/journal.pbio.3001185 · Cited by 21
“Over evolutionary time, increased levels of gene expression result in a selective pressure for accurate and efficient translation [26–30] and increased mRNA stability [31,32].”
Endogenous p53 expression in human and mouse is not regulated by its 3′UTR
Mitschka, S., & Mayr, C. (2021) · eLife · doi:10.7554/elife.65700 · Cited by 26
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Callens, M., Scornavacca, C., & Bedhomme, S. (2021) · Microbial Genomics · doi:10.1099/mgen.0.000587 · Cited by 25
“Furthermore, mRNAs containing non-optimal codons are found to be less stable than their synonymous equivalents using optimal codons (Presnyak et al. 2015).”
Determinants of the temperature adaptation of mRNA degradation
Jaquet, V., Wallerich, S., Voegeli, S., Túrós, D., Viloria, E. C., & Becskei, A. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab1261 · Cited by 25
“Codons explain a large proportion of variation in the mRNA half-lives under standard conditions, and mRNAs enriched in certain codons have longer half-lives (8,16).”
InfluentialGenes enriched in A/T-ending codons are co-regulated and conserved across mammals
Benisty, H., Hernandez‐Alias, X., Weber, M. L., Anglada-Girotto, M., Mantica, F., Radusky, L., Senger, G., Calvet, F., Weghorn, D., Irimia, M., et al. (2023) · Cell Systems · doi:10.1016/j.cels.2023.02.002 · Cited by 25
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“In particular, these key vaccine properties are largely affected by the RNA sequence and structure, both of which can be manipulated and optimized [2,32,51,52].”
BackgroundNucleosomal signatures impose nucleosome positioning in coding and noncoding sequences in the genomePreprint
González, S., García, A., Vázquez, E., Serrano, R., Sánchez, M., Quintales, L. A. M., & Antequera, F. (2016) · Genome Research · doi:10.1101/gr.207241.116 · Cited by 25
“S4) suggests the intriguing possibility that, in addition to modulating the stability of mRNA and its rate of translation (Plotkin and Kudla 2011; Presnyak et al. 2015), the distribution of synonymous codons might also contribute to nucleosome positioningalongORFs.”
Adaptation and Conservation throughout the Drosophila melanogaster Life-Cycle
Coronado‐Zamora, M., Salvador‐Martínez, I., Castellano, D., Barbadilla, A., & Salazar‐Ciudad, I. (2019) · Genome Biology and Evolution · doi:10.1093/gbe/evz086 · Cited by 23
A synonymous mutation in IGF-1 impacts the transcription and translation process of gene expression
Wang, S. Y., Cheng, Y., Liu, S. C., Xu, Y. X., Gao, Y., Wang, C., Wang, Z. G., Feng, T., Lu, G., Song, J., et al. (2021) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2021.08.007 · Cited by 24
Vaccines against SARS-CoV-2 variants and future pandemics
Park, T., Hwang, H., Moon, S., Kang, S. G., Song, S., Kim, Y. H., Kim, H., Ko, E., Yoon, S., Kang, S., et al. (2022) · Expert Review of Vaccines · doi:10.1080/14760584.2022.2110075 · Cited by 23
“of the more abundant tRNA species [64].”
Oligodendrocyte differentiation alters tRNA modifications and codon optimality-mediated mRNA decay
Martin, S., Allan, K. C., Pinkard, O. W., Sweet, T. J., Tesar, P. J., & Coller, J. (2022) · Nature Communications · doi:10.1038/s41467-022-32766-3 · Cited by 25
Self-citationGlobal regulation via modulation of ribosome pausing by the ABC-F protein EttA
Ousalem, F., Ngo, S., Oïffer, T., Omairi‐Nasser, A., Hamon, M., Monlezun, L., & Boël, G. (2024) · Nature Communications · doi:10.1038/s41467-024-50627-z · Cited by 24
Brown, A. P. C., Arias‐Rodríguez, L., Yee, M., Tobler, M., & Kelley, J. L. (2018) · Genome Biology and Evolution · doi:10.1093/gbe/evy198 · Cited by 27
Human DDX6 regulates translation and decay of inefficiently translated mRNAs
Weber, R., & Chang, C.-T. (2024) · eLife · doi:10.7554/elife.92426 · Cited by 23
Harnessing mRNA-lipid nanoparticles as innovative therapies for autoimmune diseases
Razavi, R., Kegel, M., Muscat-Rivera, J., Weissman, D., & Melamed, J. R. (2025) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2025.101566 · Cited by 28
“18,19 22 Modified nucleosides represent a key technology enabling the clinical translation of mRNA therapeutics.”
Araújo, D. S., De-Paula, R. B., Tomé, L. M. R., Quintanilha‐Peixoto, G., Salvador-Montoya, C. A., Del‐Bem, L., Badotti, F., Azevedo, V., Brenig, B., Aguiar, E. R. G. R., et al. (2021) · Mitochondrion · doi:10.1016/j.mito.2021.02.002 · Cited by 23
Macroevolutionary divergence of gene expression driven by selection on protein abundance
Cope, A. L., Schraiber, J. G., & Pennell, M. W. (2025) · Science · doi:10.1126/science.ads2658 · Cited by 20
Frequent GU wobble pairings reduce translation efficiency in Plasmodium falciparum
Chan, S. C.-L., Ch’ng, J.-H., Wahlgren, M., & Thutkawkorapin, J. (2017) · Scientific Reports · doi:10.1038/s41598-017-00801-9 · Cited by 23
Synonymous Codon Usage Controls Various Molecular Aspects
Im, E.-H., & Choi, S. S. (2017) · Genomics & Informatics · doi:10.5808/gi.2017.15.4.123 · Cited by 23
Nanoparticle-based delivery platforms for mRNA vaccine development
Okay, S., Özcan, Ö. Ö., & Karahan, M. (2020) · AIMS Biophysics · doi:10.3934/biophy.2020023 · Cited by 23
“Codon modifications in protein coding regions of mRNA sequences can significantly increase protein expression levels [32,33].”
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Synonymous Variants: Necessary Nuance in Our Understanding of Cancer Drivers and Treatment Outcomes
Kaissarian, N. M., Meyer, D., & Kimchi‐Sarfaty, C. (2022) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djac090 · Cited by 21
mRNA delivery technologies: Toward clinical translation
Gómez-Aguado, I., Rodríguez-Castejón, J., Beraza-Millor, M., Rodríguez‐Gascón, A., del Pozo‐Rodríguez, A., & Solinís, M. Á. (2022) · International review of cytology · doi:10.1016/bs.ircmb.2022.04.010 · Cited by 23
Munk, M., Villalobo, E., Villalobo, A., & Berchtold, M. W. (2022) · Cell Calcium · doi:10.1016/j.ceca.2022.102656 · Cited by 23
“[114], studying yeast codon usage, introduced the codon stabilization coefficient (CSC) as a way to give each codon a score, which links the codon usage of mRNA to its half-life.”
BackgroundHao, J., Liang, Y., Ping, J., Li, J., Shi, W., Su, Y., & Wang, T. (2022) · BMC Plant Biology · doi:10.1186/s12870-022-03960-8 · Cited by 22
Quality control of protein synthesis in the early elongation stage
Nagao, A., Nakanishi, Y., Yamaguchi, Y., Mishina, Y., Karoji, M., Toya, T., Fujita, T., Iwasaki, S., Miyauchi, K., Sakaguchi, Y., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-38077-5 · Cited by 24
“Therefore, the optimal codon usage contributes to ef fi cient translation 100,106 – 108 , proper protein folding 109 – 111 and regulation of mRNA stability 112 – 115 .”
Analysis of synonymous codon usage in Zika virus
Hussain, S., & Rasool, S. T. (2017) · Acta Tropica · doi:10.1016/j.actatropica.2017.06.006 · Cited by 22
mRNA medicine: Recent progresses in chemical modification, design, and engineering
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Decoding Codon Bias: The Role of tRNA Modifications in Tissue-Specific Translation
Ando, D., Rashad, S., Begley, T. J., Endo, H., Aoki, M., Dedon, P. C., & Niizuma, K. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26020706 · Cited by 21
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“For instance, in yeast, codons AAG and CAA were considered optimal codons, which had a faster ribosome translocation rate, whereas AAA and CAG were nonoptimal codons with a slower translocation rate (Presnyak et al., 2015).”
Höllerer, S., & Jeschek, M. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad040 · Cited by 21
“Similar to previous studies (e.g. (29,30,34,38,54,101)), our data confirmed a strong dependence of the rTR on the N-terminal CDS and a decreasing impact of codons with increasing distance to the start codon (Figures 2, 4B, C).”
The central role of translation elongation in response to stress
Barros, G. C., Guerrero, S., & Silva, G. M. (2023) · Biochemical Society Transactions · doi:10.1042/bst20220584 · Cited by 22
Molecular Evolution of Protein Sequences and Codon Usage in Monkeypox Viruses
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“This bias is widely recognized for its considerable influence to the efficiency and precision of mRNA translation [35–38], mRNA stability [39], and peptide conformation [40,41], potentially impacting the adaptability and fitness of organisms.”
BackgroundBertalovitz, A. C., Osterbur, M. L., & McDonald, T. V. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.001805 · Cited by 22
“Although an exact mechanism defining mRNA stability has not been established, it has been shown that less optimal codon use has been shown to result in mRNA with shorter half-lives (28, 29).”
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RNA control in pain: Blame it on the messenger
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“While this is an intuitive solution, long-term changes require sustained responses that appear to be driven largely by translation of mRNA (Alvarez, 2001; Alvarez, Giuditta, & Koenig, 2000; Khoutorsky et al., 2015; Price & Geranton, 2009).”
BackgroundPolyA tracks, polybasic peptides, poly‐translational hurdles
Arthur, L., & Djuranović, S. (2018) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1486 · Cited by 21
“…(eEF2) and release factors (eRF1 and eRF3) in “stop-carry on” translation by 2A peptides, one should be cautious on how 2A peptides impact results, complicate analysis, and change overall context of tested polybasic sequences (Doronina et al., 2008; Machida et al., 2014; Roulston et al., 2016).”
BackgroundPromoter architecture determines cotranslational regulation of mRNAPreprint
Espinar, L., Schikora-Tamarit, M. À., Domingo, J., & Carey, L. B. (2018) · Genome Research · doi:10.1101/gr.230458.117 · Cited by 22
“2003)) and 3’UTR length, both of which require active translation to be interpreted by the cell (Gardin et al. 2014; Kervestin and Jacobson 2012; Presnyak et al. 2015), have more importance in a model trained on RPL4Apr data compared to GALLpr data (Fig.”
ResultLegrand, A., Dahoui, C., De La Myre Mory, C., Noy, K., Guiguettaz, L., Versapuech, M., Loyer, C., Pillon, M., Wcislo, M., Guéguen, L., et al. (2024) · PLOS Biology · doi:10.1371/journal.pbio.3002696 · Cited by 18
Emergence of a “Cyclosome” in a Primitive Network Capable of Building “Infinite” Proteins
Jacques Demongeot, A., & Norris, V. (2019) · Life · doi:10.3390/life9020051 · Cited by 20
“If we consider other subsequences of AL, we find many repeated motifs, such as AATGG [37] and GATG [38] from human microsatellites, AGAT from vertebrate repeated UTR motifs [39], and CCATTCA from the Alpha Satellite of Human Chromosome 17 [40] and from the HMG box (High Mobility Group Box, a protein domain involved in…”
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Sustainable and high-level microbial production of plant hemoglobin in Corynebacterium glutamicum
Wang, M., Shi, Z. Q., Gao, N., Zhou, Y., Ni, X., Chen, J., Liu, J., Zhou, W., Guo, X., Xin, B., et al. (2023) · Biotechnology for Biofuels and Bioproducts · doi:10.1186/s13068-023-02337-9 · Cited by 21
“coli [43, 44], and little information is available for C.”
BackgroundHypoxia and inflammation induce synergistic transcriptome turnover in macrophages
Courvan, E. M. C., & Parker, R. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114452 · Cited by 23
Dengue virus preferentially uses human and mosquito non-optimal codons
Castellano, L. A., McNamara, R. J., Pallarés, H. M., Gamarnik, A. V., Alvarez, D. E., & Bazzini, A. (2024) · Molecular Systems Biology · doi:10.1038/s44320-024-00052-7 · Cited by 20
“For each codon, the codon stability coef fi cient (CSC) was calculated as the Pearson correlation between mRNA stability and codon occurrence (Presnyak et al, 2015).”
InfluentialSynthesis at the Speed of Codons
Koutmou, K. S., Radhakrishnan, A., & Green, R. (2015) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2015.10.005 · Cited by 20
“Importantly, a recent study of particular interest demonstrated that codon choice (optimality) does directly impact gene expression by dictating mRNA stability in yeast [8]; however, as this study focused on mRNA decay, no direct connection was made to rates of ribosome movement on codons.”
BackgroundVillanueva, E., Martí-Solano, M., & Fillat, C. (2016) · Scientific Reports · doi:10.1038/srep27546 · Cited by 20
Glutamine Codon Usage and polyQ Evolution in Primates Depend on the Q Stretch Length
Mier, P., & Andrade-Navarro, M. A. (2018) · Genome Biology and Evolution · doi:10.1093/gbe/evy046 · Cited by 20
What Has a Century of Quantitative Genetics Taught Us About Nature's Genetic Tool Kit?
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Estimating the predictive power of silent mutations on cancer classification and prognosis
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Landscape of the Dark Transcriptome Revealed Through Re-mining Massive RNA-Seq Data
Li, J., Singh, U., Arendsee, Z. W., & Wurtele, E. S. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.722981 · Cited by 18
Codon optimality and mRNA decay
Harigaya, Y., & Parker, R. (2016) · Cell Research · doi:10.1038/cr.2016.127 · Cited by 19
Evolution and codon usage bias of mitochondrial and nuclear genomes in Aspergillus section Flavi
Hugaboom, M. B., Hatmaker, E. A., LaBella, A. L., & Rokas, A. (2022) · G3 Genes Genomes Genetics · doi:10.1093/g3journal/jkac285 · Cited by 19
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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