Silent Substitutions Predictably Alter Translation Elongation Rates and Protein Folding Efficiencies
Open accessAbstract
Genetic code redundancy allows most amino acids to be encoded by multiple codons that are non-randomly distributed along coding sequences. An accepted theory explaining the biological significance of such non-uniform codon selection is that codons are translated at different speeds. Thus, varying codon placement along a message may confer variable rates of polypeptide emergence from the ribosome, which may influence the capacity to fold toward the native state. Previous studies report conflicting results regarding whether certain codons correlate with particular structural or folding properties of the encoded protein. This is partly due to different criteria traditionally utilized for predicting translation speeds of codons, including their usage frequencies and the concentration of tRNA species capable of decoding them, which do not always correlate. Here, we developed a metric to predict organism-specific relative translation rates of codons based on the availability of tRNA decoding mechanisms: Watson-Crick, non-Watson-Crick or both types of interactions. We determine translation rates of messages by pulse-chase analyses in living Escherichia coli cells and show that sequence engineering based on these concepts predictably modulates translation rates in a manner that is superior to codon usage frequency, which occur during the elongation phase, and significantly impacts folding of the encoded polypeptide. Finally, we demonstrate that sequence harmonization based on expression host tRNA pools, designed to mimic ribosome movement of the original organism, can significantly increase the folding of the encoded polypeptide. These results illuminate how genetic code degeneracy may function to specify properties beyond amino acid encoding, including folding.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Replacement of rare codons must be used judiciously because, for some proteins, the slower translation rate of rare codons is necessary for proper protein folding.
“Although replacement of rare codons is an attractive optimization strategy, it must be used judiciously. This is because, in the case of some proteins, the slower translation rate of rare codons is necessary for proper protein folding22.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [22]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A "Silent" Polymorphism in the <i>MDR</i> 1 Gene Changes Substrate Specificity
Kimchi-Sarfaty, C., Oh, J. M., Kim, I.-W., Sauna, Z. E., Calcagno, A. M., Ambudkar, S. V., & Gottesman, M. M. (2007) · Science · doi:10.1126/science.1135308 · Cited by 2,416 · see citing works
Codon—anticodon pairing: The wobble hypothesis
Crick, F. H. C. (1966) · Journal of Molecular Biology · doi:10.1016/s0022-2836(66)80022-0 · Cited by 2,029 · see citing works
Codon usage and tRNA content in unicellular and multicellular organisms.
Ikemura, T. (1985) · Molecular Biology and Evolution · doi:10.1093/oxfordjournals.molbev.a040335 · Cited by 1,710 · see citing works
Coding-Sequence Determinants of Gene Expression in <i>Escherichia coli</i>
Kudla, G., Murray, A. W., Tollervey, D., & Plotkin, J. B. (2009) · Science · doi:10.1126/science.1170160 · Cited by 1,458 · see citing works
Translational control of gene expression
Sonenberg, N., Hershey, J. W. B., & Mathews, M. B. (2000) · Cold Spring Harbor Laboratory eBooks · Cited by 1,379 · see citing works
Translational control of gene expression
Hannig, E. M. (2001) · BioEssays · doi:10.1002/bies.1108 · Cited by 1,194 · see citing works
GtRNAdb: a database of transfer RNA genes detected in genomic sequence
Chan, P. P., & Lowe, T. M. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn787 · Cited by 867 · see citing works
Regulation of translation via mRNA structure in prokaryotes and eukaryotes
Kozak, M. (2005) · Gene · doi:10.1016/j.gene.2005.06.037 · Cited by 747 · see citing works
Tissue-Specific Differences in Human Transfer RNA Expression
Dittmar, K. A., Goodenbour, J. M., & Pan, T. (2006) · PLoS Genetics · doi:10.1371/journal.pgen.0020221 · Cited by 601 · see citing works
Translation is a non-uniform process
Varenne, S., Buc, J., Lloubès, R., & Lazdunski, C. J. (1984) · Journal of Molecular Biology · doi:10.1016/0022-2836(84)90027-5 · Cited by 384 · see citing works
Kinetic determinants of high-fidelity tRNA discrimination on the ribosome.
Gromadski, K. B., & Rodnina, M. (2004) · Molecules and Cells · doi:10.1016/s1097-2765(04)00005-x · Cited by 377 · see citing works
Grosjean, H., de Crécy‐Lagard, V., & Marck, C. (2009) · FEBS Letters · doi:10.1016/j.febslet.2009.11.052 · Cited by 298 · see citing works
tRNA over-expression in breast cancer and functional consequences
Pavon-Eternod, M., Gomes, S., Geslain, R., Dai, Q., Rosner, M. R., & Pan, T. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp787 · Cited by 296 · see citing works
Absolute in vivo translation rates of individual codons in Escherichia coli
Sørensen, M. A., & Pedersen, S. B. (1991) · Journal of Molecular Biology · doi:10.1016/0022-2836(91)90211-n · Cited by 271 · see citing works
Escherichia coli ribosomes translate in vivo with variable rate.
Pedersen, S. B. (1984) · The EMBO Journal · doi:10.1002/j.1460-2075.1984.tb02227.x · Cited by 270 · see citing works
Rates of aminoacyl-tRNA selection at 29 sense codons in vivo
Curran, J. F., & Yarus, M. (1989) · Journal of Molecular Biology · doi:10.1016/0022-2836(89)90170-8 · Cited by 239 · see citing works
Bringing order to translation: the contributions of transfer RNA anticodon‐domain modifications
Agris, P. F. (2008) · EMBO Reports · doi:10.1038/embor.2008.104 · Cited by 233 · see citing works
Wobble base-pairing slows in vivo translation elongation in metazoans
Stadler, M. R., & Fire, A. Z. (2011) · RNA · doi:10.1261/rna.02890211 · Cited by 188 · see citing works
Slowing Bacterial Translation Speed Enhances Eukaryotic Protein Folding Efficiency
Siller, E., DeZwaan, D. C., Anderson, J. F., Freeman, B., & Barral, J. M. (2010) · Journal of Molecular Biology · doi:10.1016/j.jmb.2009.12.042 · Cited by 170 · see citing works
Self-citationThe Kinetics of Ribosomal Peptidyl Transfer Revisited
Johansson, M., Bouakaz, E., Lovmar, M., & Ehrenberg, M. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.04.010 · Cited by 147 · see citing works
mRNA Composition and Control of Bacterial Gene Expression
Liang, S., Xu, Y. C., Dennis, P. P., & Bremer, H. (2000) · Journal of Bacteriology · doi:10.1128/jb.182.11.3037-3044.2000 · Cited by 138 · see citing works
Ribosome kinetics and aa-tRNA competition determine rate and fidelity of peptide synthesis
Fluitt, A. M., Pienaar, E., & Viljoen, H. J. (2007) · Computational Biology and Chemistry · doi:10.1016/j.compbiolchem.2007.07.003 · Cited by 135 · see citing works
1 Origins and Principles of Translational ControlPreprint
Mathews, M. B., Sonenberg, N., & Hershey, J. W. B. (2007) · Cold Spring Harbor Monograph Archive · doi:10.1101/087969767.48.1 · Cited by 119 · see citing works
Codon pairs in the genome of Escherichia coli
Boycheva, S., Chkodrov, G., & Ivanov, I. G. (2003) · Bioinformatics · doi:10.1093/bioinformatics/btg082 · Cited by 81 · see citing works
GENETIC CODE REDUNDANCY AND ITS INFLUENCE ON THE ENCODED POLYPEPTIDES
Spencer, P. S., & Barral, J. M. (2012) · Computational and Structural Biotechnology Journal · doi:10.5936/csbj.201204006 · Cited by 56 · see citing works
Self-citationThe imprint of codons on protein structure
Deane, C. M., & Saunders, R. (2011) · Biotechnology Journal · doi:10.1002/biot.201000329 · Cited by 21 · see citing works
Endoh, T., Kawasaki, Y., & Sugimoto, N. (2011) · Analytical Chemistry · doi:10.1021/ac202712g · Cited by 15 · see citing works
Determination of the Peptide Elongation Rate In Vivo
Sørensen, M. A., & Pedersen, S. B. (2003) · Humana Press eBooks · doi:10.1385/0-89603-397-x:129 · Cited by 9 · see citing works
Flagged first, then by citations
2 of the 30 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
mRNA vaccines for infectious diseases: principles, delivery and clinical translation
Chaudhary, N., Weissman, D., & Whitehead, K. A. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00283-5 · Cited by 1,555 · see citing works
Molecular Chaperone Functions in Protein Folding and Proteostasis
Kim, Y., Hipp, M. S., Bracher, A., Hayer-Hartl, M. K., & Hartl, F. U. (2013) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060208-092442 · Cited by 1,468 · see citing works
In vivo aspects of protein folding and quality control
Balchin, D., Hayer-Hartl, M. K., & Hartl, F. U. (2016) · Science · doi:10.1126/science.aac4354 · Cited by 1,432 · see citing works
Codon optimality, bias and usage in translation and mRNA decay
Hanson, G., & Coller, J. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.91 · Cited by 825 · see citing works
Codon Bias as a Means to Fine-Tune Gene Expression
Quax, T. E. F., Claassens, N. J., Söll, D. G., & John van der, O. O. S. T. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.05.035 · Cited by 779 · see citing works
Yu, C., Dang, Y., Zhou, Z., Wu, C., Zhao, F., Sachs, M. S., & Liu, Y. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.07.018 · Cited by 605 · see citing works
Zhou, Z., Dang, Y., Zhou, M., Li, L., Yu, C., Fu, J., Chen, S., & Liu, Y. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1606724113 · Cited by 441 · see citing works
Codon influence on protein expression in E. coli correlates with mRNA levels
Boël, G., Letso, R. R., Neely, H., Price, W. N., Wong, K., Su, M., Luff, J. D., Valecha, M., Everett, J. K., Acton, T., et al. (2016) · Nature · doi:10.1038/nature16509 · Cited by 429 · see citing works
Non-optimal codon usage affects expression, structure and function of clock protein FRQ
Zhou, M., Guo, J., Cha, J., Chae, M., Chen, S., Barral, J. M., Sachs, M. S., & Liu, Y. (2013) · Nature · doi:10.1038/nature11833 · Cited by 418 · see citing works
Self-citationHunt, R., Simhadri, V. L., Iandoli, M., Sauna, Z. E., & Kimchi‐Sarfaty, C. (2014) · Trends in Genetics · doi:10.1016/j.tig.2014.04.006 · Cited by 386 · see citing works
Tailoring mRNA Vaccine to Balance Innate/Adaptive Immune Response
Linares-Fernández, S., Lacroix, C., Exposito, J.-Y., & Verrier, B. (2020) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2019.10.002 · Cited by 376 · see citing works
A critical analysis of codon optimization in human therapeutics
Mauro, V. P., & Chappell, S. A. (2014) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2014.09.003 · Cited by 343 · see citing works
Roles for Synonymous Codon Usage in Protein Biogenesis
Chaney, J. L., & Clark, P. L. (2015) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-060414-034333 · Cited by 306 · see citing works
The DEAD-Box Protein Dhh1p Couples mRNA Decay and Translation by Monitoring Codon Optimality
Radhakrishnan, A., Chen, Y.-H., Martin, S., Alhusaini, N., Green, R., & Coller, J. (2016) · Cell · doi:10.1016/j.cell.2016.08.053 · Cited by 279 · see citing works
Translation in ProkaryotesPreprint
Rodnina, M. V. (2018) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a032664 · Cited by 279 · see citing works
From influenza to COVID-19: Lipid nanoparticle mRNA vaccines at the frontiers of infectious diseases
Pilkington, E. H., Suys, E. J. A., Trevaskis, N. L., Wheatley, A. K., Zukancic, D., Algarni, A., Al-Wassiti, H. A., Davis, T. P., Pouton, C. W., Kent, S. J., et al. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.06.023 · Cited by 265 · see citing works
A code within the genetic code: codon usage regulates co-translational protein folding
Liu, Y. (2020) · Cell Communication and Signaling · doi:10.1186/s12964-020-00642-6 · Cited by 252 · see citing works
Differential Scales of Protein Quality Control
Wolff, S., Weissman, J. S., & Dillin, A. G. (2014) · Cell · doi:10.1016/j.cell.2014.03.007 · Cited by 243 · see citing works
Synonymous but Not Silent: The Codon Usage Code for Gene Expression and Protein Folding
Liu, Y., Yang, Q., & Zhao, F. (2021) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-071320-112701 · Cited by 242 · see citing works
Introduction to Population Biology
Neal, D. (2003) · Cambridge University Press eBooks · doi:10.1017/9781139107976 · Cited by 234 · see citing works
Local slowdown of translation by nonoptimal codons promotes nascent-chain recognition by SRP in vivo
Pechmann, S., Chartron, J. W., & Frydman, J. (2014) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2919 · Cited by 215 · see citing works
AAV-based in vivo gene therapy for neurological disorders
Ling, Q., Herstine, J. A., Bradbury, A. M., & Gray, S. J. (2023) · Nature Reviews Drug Discovery · doi:10.1038/s41573-023-00766-7 · Cited by 206 · see citing works
Translational tuning optimizes nascent protein folding in cells
Kim, S. J., Yoon, J. S., Shishido, H., Yang, Z., Rooney, L. A., Barral, J. M., & Skach, W. R. (2015) · Science · doi:10.1126/science.aaa3974 · Cited by 193 · see citing works
Self-citationWang, Y., Kumari, M., Chen, G., Hong, M.-H., Yuan, J. P., Tsai, J.-L., & Wu, H. (2023) · Journal of Biomedical Science · doi:10.1186/s12929-023-00977-5 · Cited by 183 · see citing works
Sander, I. M., Chaney, J. L., & Clark, P. L. (2014) · Journal of the American Chemical Society · doi:10.1021/ja411302m · Cited by 171 · see citing works
Stein, K. C., & Frydman, J. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.rev118.002814 · Cited by 160 · see citing works
Co-translational mechanisms of protein maturation
Gloge, F., Becker, A. H., Krämer, G., & Bukau, B. (2013) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2013.11.004 · Cited by 136 · see citing works
Decoding mechanisms by which silent codon changes influence protein biogenesis and function
Bali, V., & Bebok, Z. M. (2015) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2015.03.011 · Cited by 133 · see citing works
Role of mRNA structure in the control of protein folding
Faure, G., Ogurtsov, A. Y., Shabalina, S. A., & Koonin, E. V. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw671 · Cited by 134 · see citing works
Connections Underlying Translation and mRNA Stability
Radhakrishnan, A., & Green, R. (2016) · Journal of Molecular Biology · doi:10.1016/j.jmb.2016.05.025 · Cited by 131 · see citing works
Zhao, F., Yu, C.-H., & Liu, Y. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx501 · Cited by 120 · see citing works
Nonoptimal codon usage influences protein structure in intrinsically disordered regions
Zhou, M., Wang, T., Fu, J., Xiao, G., & Liu, Y. (2015) · Molecular Microbiology · doi:10.1111/mmi.13079 · Cited by 109 · see citing works
Current landscape of mRNA technologies and delivery systems for new modality therapeutics
Lu, R., Hsu, H.-E., Perez, S. J. L. P., Kumari, M., Chen, G., Hong, M.-H., Lin, Y.-S., Liu, C.-H., Ko, S.-H., Concio, C. A. P., et al. (2024) · Journal of Biomedical Science · doi:10.1186/s12929-024-01080-z · Cited by 113 · see citing works
Understanding the Influence of Codon Translation Rates on Cotranslational Protein Folding
O’Brien, E. P., Ciryam, P., Vendruscolo, M., & Dobson, C. M. (2014) · Accounts of Chemical Research · doi:10.1021/ar5000117 · Cited by 104 · see citing works
Control of translation elongation in health and disease
Knight, J. R. P., Garland, G. D., Pöyry, T. A. A., Mead, E. J., Vlahov, N., Sfakianos, A., Grosso, S., Hedayioglu, F. D. L., Mallucci, G. R., von der Haar, T., et al. (2020) · Disease Models & Mechanisms · doi:10.1242/dmm.043208 · Cited by 93 · see citing works
Evidence of evolutionary selection for cotranslational folding
Jacobs, W. M., & Shakhnovich, E. I. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1705772114 · Cited by 98 · see citing works
Ribosome Stoichiometry: From Form to Function
Emmott, E., Jovanović, M., & Slavov, N. (2018) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2018.10.009 · Cited by 95 · see citing works
How synonymous mutations alter enzyme structure and function over long timescales
Jiang, Y., Neti, S. S., Sitarik, I. M., Pradhan, P., To, P., Xia, Y., Fried, S. D., Booker, S. J., & O’Brien, E. P. (2022) · Nature Chemistry · doi:10.1038/s41557-022-01091-z · Cited by 93 · see citing works
Chadani, Y., Niwa, T., Izumi, T., Sugata, N., Nagao, A., Suzuki, T., Chiba, S., Ito, K., & Taguchi, H. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.10.020 · Cited by 85 · see citing works
O’Brien, E. P., Vendruscolo, M., & Dobson, C. M. (2014) · Nature Communications · doi:10.1038/ncomms3988 · Cited by 89 · see citing works
mRNA nanodelivery systems: targeting strategies and administration routes
Yuan, M., Han, Z., Liang, Y., Sun, Y., He, B., Chen, W., & Fan, L. (2023) · Biomaterials Research · doi:10.1186/s40824-023-00425-3 · Cited by 90 · see citing works
AAV vector development, back to the future
Suárez-Amarán, L., Song, L., Tretiakova, A. P., Mikhail, S., & Samulski, R. J. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.03.064 · Cited by 87 · see citing works
Formyl-methionine as a degradation signal at the N-termini of bacterial proteins
Piatkov, K. I., Vu, T. T. M., Hwang, C., & Varshavsky, A. J. (2015) · Microbial Cell · doi:10.15698/mic2015.10.231 · Cited by 84 · see citing works
Protein Elongation, Co-translational Folding and Targeting
Rodnina, M. V., & Wintermeyer, W. (2016) · Journal of Molecular Biology · doi:10.1016/j.jmb.2016.03.022 · Cited by 82 · see citing works
mRNA vaccines: the most recent clinical applications of synthetic mRNA
Kwon, S., Kwon, M., Im, S., Lee, K., & Lee, H. (2022) · Archives of Pharmacal Research · doi:10.1007/s12272-022-01381-7 · Cited by 81 · see citing works
Altering SARS Coronavirus Frameshift Efficiency Affects Genomic and Subgenomic RNA Production
Plant, E. P., Sims, A. M., Baric, R. S., Dinman, J. D., & Taylor, D. R. (2013) · Viruses · doi:10.3390/v5010279 · Cited by 77 · see citing works
Rodríguez, A., Wright, G. S., Emrich, S., & Clark, P. L. (2017) · Protein Science · doi:10.1002/pro.3336 · Cited by 75 · see citing works
Zhou, Z., Dang, Y., Zhou, M., Yuan, H., & Liu, Y. (2018) · eLife · doi:10.7554/elife.33569 · Cited by 69 · see citing works
Yang, Q., Yu, C., Zhao, F., Dang, Y., Wu, C., Xie, P., Sachs, M. S., & Liu, Y. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz710 · Cited by 70 · see citing works
Jacobson, G. N., & Clark, P. L. (2016) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2016.06.002 · Cited by 69 · see citing works
Codon usage affects the structure and function of the Drosophila circadian clock protein PERIODPreprint
Fu, J., Murphy, K. A., Zhou, M., Li, Y. H., Lam, V. H., Tabuloc, C. A., Chiu, J. C., & Liu, Y. (2016) · Genes & Development · doi:10.1101/gad.281030.116 · Cited by 67 · see citing works
Saito, K., Horikawa, W., & Ito, K. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1005197 · Cited by 67 · see citing works
The Effects of Codon Usage on Protein Structure and Folding
Moss, M. J., Chamness, L. M., & Clark, P. L. (2023) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-030722-020555 · Cited by 64 · see citing works
Non-equilibrium coupling of protein structure and function to translation–elongation kinetics
Sharma, A. K., & O’Brien, E. P. (2018) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2018.01.005 · Cited by 62 · see citing works
The ribosome destabilizes native and non‐native structures in a nascent multidomain protein
Liu, K., Rehfus, J. E., Mattson, E., & Kaiser, C. (2017) · Protein Science · doi:10.1002/pro.3189 · Cited by 61 · see citing works
Claassens, N. J., Siliakus, M. F., Spaans, S. K., Creutzburg, S. C. A., Nijsse, B., Schaap, P. J., Quax, T. E. F., & John van der, O. O. S. T. (2017) · PLoS ONE · doi:10.1371/journal.pone.0184355 · Cited by 61 · see citing works
The effects of codon bias and optimality on mRNA and protein regulation
Hia, F., & Takeuchi, O. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03685-7 · Cited by 59 · see citing works
Nissley, D. A., Jiang, Y., Trovato, F., Sitarik, I. M., Narayan, K. B., To, P., Xia, Y., Fried, S. D., & O’Brien, E. P. (2022) · Nature Communications · doi:10.1038/s41467-022-30548-5 · Cited by 59 · see citing works
Codon usage regulates human KRAS expression at both transcriptional and translational levels
Fu, J., Dang, Y., Counter, C. M., & Liu, Y. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.004908 · Cited by 58 · see citing works
The functional relevance of somatic synonymous mutations in melanoma and other cancers
Gotea, V., Gartner, J. J., Qutob, N., Elnitski, L. L., & Samuels, Y. (2015) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12413 · Cited by 58 · see citing works
Context effects of genetic code expansion by stop codon suppression
Chemla, Y., Ozer, E., Algov, I., & Alfonta, L. (2018) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2018.07.012 · Cited by 57 · see citing works
Bi, H., Xu, C., Bao, Y., Zhang, C., Wang, K., Zhang, Y., Wang, M., Chen, B., Fang, Y., & Tan, T. (2023) · Bioresource Technology · doi:10.1016/j.biortech.2023.129171 · Cited by 57 · see citing works
Westhof, É., Yusupov, M., & Yusupova, G. Z. (2014) · F1000Prime Reports · doi:10.12703/p6-19 · Cited by 54 · see citing works
Ribosomal Stalk Protein Silencing Partially Corrects the ΔF508-CFTR Functional Expression Defect
Veit, G., Oliver, K. E., Apaja, P. M., Perdomo, D., Bidaud-Meynard, A., Lin, S.-T., Guo, J., Icyuz, M., Sorscher, E. J., Hartman, J. L., et al. (2016) · PLoS Biology · doi:10.1371/journal.pbio.1002462 · Cited by 55 · see citing works
Mechanism of the Neurospora Circadian Clock, a FREQUENCY-centric View
Cha, J., Zhou, M., & Liu, Y. (2014) · Biochemistry · doi:10.1021/bi5005624 · Cited by 54 · see citing works
Genetic Code-guided Protein Synthesis and Folding in Escherichia coli
Hu, S., Wang, M., Cai, G., & He, M. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.467977 · Cited by 54 · see citing works
Lian, X., Guo, J., Gu, W., Cui, Y., Zhong, J., Jin, J., He, Q., Wang, T., & Zhang, G. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1005901 · Cited by 48 · see citing works
Modular Construction of a Functional Artificial Epothilone Polyketide Pathway
Oßwald, C., Zipf, G., Schmidt, G., Maier, J., Bernauer, H. S., Müller, R., & Wenzel, S. C. (2012) · ACS Synthetic Biology · doi:10.1021/sb300080t · Cited by 47 · see citing works
Shi, F., Yao, Y., Bin, Y., Zheng, C.-H., & Xia, J. (2019) · BMC Medical Genomics · doi:10.1186/s12920-018-0455-6 · Cited by 47 · see citing works
GTPBP1 resolves paused ribosomes to maintain neuronal homeostasis
Terrey, M., Adamson, S. I., Gibson, A. L., Deng, T. Z., Ishimura, R., Chuang, J. H., & Ackerman, S. L. (2020) · eLife · doi:10.7554/elife.62731 · Cited by 47 · see citing works
Nissley, D. A., Sharma, A. K., Ahmed, N., Friedrich, U. A., Krämer, G., Bukau, B., & O’Brien, E. P. (2016) · Nature Communications · doi:10.1038/ncomms10341 · Cited by 46 · see citing works
Assessing optimal: inequalities in codon optimization algorithms
Ranaghan, M. J., Li, J. J., Laprise, D., & Garvie, C. W. (2021) · BMC Biology · doi:10.1186/s12915-021-00968-8 · Cited by 45 · see citing works
Timing Is Everything: Unifying Codon Translation Rates and Nascent Proteome Behavior
Nissley, D. A., & O’Brien, E. P. (2014) · Journal of the American Chemical Society · doi:10.1021/ja510082j · Cited by 45 · see citing works
Ribosome A and P sites revealed by length analysis of ribosome profiling data
Martens, A. T., Taylor, J., & Hilser, V. J. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv200 · Cited by 44 · see citing works
Folding up and Moving on—Nascent Protein Folding on the Ribosome
Kaiser, C., & Liu, K. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2018.06.050 · Cited by 43 · see citing works
Integrated in vivo and in vitro nascent chain profiling reveals widespread translational pausing
Chadani, Y., Niwa, T., Chiba, S., Taguchi, H., & Ito, K. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1520560113 · Cited by 41 · see citing works
Genetic Drift and Effective Population Size
Neal, D. (2018) · Cambridge University Press eBooks · doi:10.1017/9781139107976.012 · Cited by 39 · see citing works
Fages‐Lartaud, M., Hundvin, K., & Hohmann‐Marriott, M. F. (2022) · The Plant Journal · doi:10.1111/tpj.15970 · Cited by 39 · see citing works
dbDSM: a manually curated database for deleterious synonymous mutations
Wen, P., Xiao, P., & Xia, J. (2016) · Bioinformatics · doi:10.1093/bioinformatics/btw086 · Cited by 39 · see citing works
Origins of the Mechanochemical Coupling of Peptide Bond Formation to Protein Synthesis
Fritch, B., Kosolapov, A., Hudson, P. S., Nissley, D. A., Woodcock, H. L., DEUTSCH, C. J., & O’Brien, E. P. (2018) · Journal of the American Chemical Society · doi:10.1021/jacs.7b11044 · Cited by 39 · see citing works
Insights into Cotranslational Nascent Protein Behavior from Computer Simulations
Trovato, F., & O’Brien, E. P. (2016) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-070915-094153 · Cited by 35 · see citing works
Lamichhane, T. N., Arimbasseri, G. A., Rijal, K., Iben, J., Wei, F., Tomizawa, K., & Maraia, R. J. (2016) · RNA · doi:10.1261/rna.054064.115 · Cited by 38 · see citing works
Differential bicodon usage in lowly and highly abundant proteins
Diambra, L. A. (2017) · PeerJ · doi:10.7717/peerj.3081 · Cited by 38 · see citing works
Sharma, A. K., Bukau, B., & O’Brien, E. P. (2015) · Journal of the American Chemical Society · doi:10.1021/jacs.5b08145 · Cited by 37 · see citing works
On the role of mRNA secondary structure in bacterial translation
Chiaruttini, C., & Guillier, M. (2019) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1579 · Cited by 37 · see citing works
Widespread non-modular overlapping codes in the coding regions*
Bergman, S., & Tuller, T. (2020) · Physical Biology · doi:10.1088/1478-3975/ab7083 · Cited by 37 · see citing works
Optimization of Translation Profiles Enhances Protein Expression and Solubility
Heß, A., Saffert, P., Liebeton, K., & Ignatova, Z. (2015) · PLoS ONE · doi:10.1371/journal.pone.0127039 · Cited by 37 · see citing works
Zhang, J., Liu, Y., Li, C., Xiao, Q., Zhang, D., Chen, Y., Rosenecker, J., Ding, X., & Guan, S. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15092182 · Cited by 39 · see citing works
Nanoformulations targeting immune cells for cancer therapy: mRNA therapeutics
Yang, W., Cao, J., Cheng, H., Chen, L., Yu, M., Chen, Y., & Cui, X. (2022) · Bioactive Materials · doi:10.1016/j.bioactmat.2022.11.014 · Cited by 36 · see citing works
CHARMING : Harmonizing synonymous codon usage to replicate a desired codon usage pattern
Wright, G. S., Rodríguez, A., Li, J., Milenković, T., Emrich, S., & Clark, P. L. (2021) · Protein Science · doi:10.1002/pro.4223 · Cited by 32 · see citing works
Hutt, D. M., Loguercio, S., Roth, D., Su, A. I., & Balch, W. E. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.003192 · Cited by 32 · see citing works
Macromolecular Protein Complexes II: Structure and Function
(2019) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-3-030-28151-9 · Cited by 31 · see citing works
Effect of mRNA/tRNA mutations on translation speed: Implications for human diseases
Davyt, M., Bharti, N., & Ignatova, Z. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.105089 · Cited by 31 · see citing works
Different types of secondary information in the genetic code
Maraia, R. J., & Iben, J. (2014) · RNA · doi:10.1261/rna.044115.113 · Cited by 30 · see citing works
Codon Bias Patterns of E. coli’s Interacting Proteins
Dilucca, M., Cimini, G., Semmoloni, A., Deiana, A., & Giansanti, A. (2015) · PLoS ONE · doi:10.1371/journal.pone.0142127 · Cited by 29 · see citing works
Does proteostasis get lost in translation? Implications for protein aggregation across the lifespan
Francisco, S., Ferreira, M., Moura, G., Soares, A. R., & Santos, M. A. S. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101119 · Cited by 30 · see citing works
Evolutionary Changes after Translational Challenges Imposed by Horizontal Gene Transfer
Bedhomme, S., Amorós-Moya, D., Valero, L., Bonifaci, N., Pujana, M. Á., & Bravo, I. G. (2019) · Genome Biology and Evolution · doi:10.1093/gbe/evz031 · Cited by 28 · see citing works
Terrey, M., Adamson, S. I., Chuang, J. H., & Ackerman, S. L. (2021) · eLife · doi:10.7554/elife.66904 · Cited by 27 · see citing works
Personalized Biochemistry and Biophysics
Kroncke, B. M., Vanoye, C. G., Meiler, J., George, A. L., & Sanders, C. R. (2015) · Biochemistry · doi:10.1021/acs.biochem.5b00189 · Cited by 27 · see citing works
Assessing cell-specific effects of genetic variations using tRNA microarrays
Polte, C., Wedemeyer, D., Oliver, K. E., Wagner, J., Bijvelds, M. J. C., Mahoney, J. E., de Jonge, H. R., Sorscher, E. J., & Ignatova, Z. (2019) · BMC Genomics · doi:10.1186/s12864-019-5864-1 · Cited by 27 · see citing works
- Authors
- Spencer, P. S., Siller, E., Anderson, J. F., & Barral, J. M.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- Corresponding author
- Barral, José M.
- Venue
- Journal of Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2012-09
- Volume
- 422
- Issue
- 3
- Pages
- 328-335
- ISSN
- 0022-2836 (ISSN-L)
- PMC
- PMC3576719
- OpenAlex
- W2094148055
- Cited by
- 278
- References
- 30
- Citations by year
- 2026: 10 · 2025: 9 · 2024: 34 · 2023: 21 · 2022: 14 · 2021: 19 · 2020: 14 · 2019: 17 · 2018: 45 · 2017: 27 · 2016: 20 · 2015: 20 · 2014: 14 · 2013: 10 · 2012: 3
- FWCI
- 6.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Molecular Biology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Francis Crick Institute
- National Institutes of Health (UL1TR000071)
- National Institute on Aging (P30AG024832)
- National Center for Research Resources (UL1RR029876)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- codon usage, translation elongation rate, protein folding, genetic code redundancy, tRNA decoding, Escherichia coli, pulse-chase analysis
- MeSH terms
- Base Sequence, Codon, Escherichia coli, Genetic Code, Molecular Sequence Data, Peptide Chain Elongation, Translational, Proteins, Ribosomes, RNA, Transfer, Protein Biosynthesis, Protein Folding, Amino Acid Substitution
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
