Codon-by-Codon Modulation of Translational Speed and Accuracy Via mRNA Folding

Rapid cell growth demands fast protein translational elongation to alleviate ribosome shortage. However, speedy elongation undermines translational accuracy because of a mechanistic tradeoff. Here we provide genomic evidence in budding yeast and mouse embryonic stem cells that the efficiency–accurac...

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Detalles Bibliográficos
Autores principales: Yang, Jian-Rong, Chen, Xiaoshu, Zhang, Jianzhi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106722/
https://www.ncbi.nlm.nih.gov/pubmed/25051069
http://dx.doi.org/10.1371/journal.pbio.1001910
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author Yang, Jian-Rong
Chen, Xiaoshu
Zhang, Jianzhi
author_facet Yang, Jian-Rong
Chen, Xiaoshu
Zhang, Jianzhi
author_sort Yang, Jian-Rong
collection PubMed
description Rapid cell growth demands fast protein translational elongation to alleviate ribosome shortage. However, speedy elongation undermines translational accuracy because of a mechanistic tradeoff. Here we provide genomic evidence in budding yeast and mouse embryonic stem cells that the efficiency–accuracy conflict is alleviated by slowing down the elongation at structurally or functionally important residues to ensure their translational accuracies while sacrificing the accuracy for speed at other residues. Our computational analysis in yeast with codon resolution suggests that mRNA secondary structures serve as elongation brakes to control the speed and hence the fidelity of protein translation. The position-specific effect of mRNA folding on translational accuracy is further demonstrated experimentally by swapping synonymous codons in a yeast transgene. Our findings explain why highly expressed genes tend to have strong mRNA folding, slow translational elongation, and conserved protein sequences. The exquisite codon-by-codon translational modulation uncovered here is a testament to the power of natural selection in mitigating efficiency–accuracy conflicts, which are prevalent in biology.
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spelling pubmed-41067222014-07-23 Codon-by-Codon Modulation of Translational Speed and Accuracy Via mRNA Folding Yang, Jian-Rong Chen, Xiaoshu Zhang, Jianzhi PLoS Biol Research Article Rapid cell growth demands fast protein translational elongation to alleviate ribosome shortage. However, speedy elongation undermines translational accuracy because of a mechanistic tradeoff. Here we provide genomic evidence in budding yeast and mouse embryonic stem cells that the efficiency–accuracy conflict is alleviated by slowing down the elongation at structurally or functionally important residues to ensure their translational accuracies while sacrificing the accuracy for speed at other residues. Our computational analysis in yeast with codon resolution suggests that mRNA secondary structures serve as elongation brakes to control the speed and hence the fidelity of protein translation. The position-specific effect of mRNA folding on translational accuracy is further demonstrated experimentally by swapping synonymous codons in a yeast transgene. Our findings explain why highly expressed genes tend to have strong mRNA folding, slow translational elongation, and conserved protein sequences. The exquisite codon-by-codon translational modulation uncovered here is a testament to the power of natural selection in mitigating efficiency–accuracy conflicts, which are prevalent in biology. Public Library of Science 2014-07-22 /pmc/articles/PMC4106722/ /pubmed/25051069 http://dx.doi.org/10.1371/journal.pbio.1001910 Text en © 2014 Yang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Yang, Jian-Rong
Chen, Xiaoshu
Zhang, Jianzhi
Codon-by-Codon Modulation of Translational Speed and Accuracy Via mRNA Folding
title Codon-by-Codon Modulation of Translational Speed and Accuracy Via mRNA Folding
title_full Codon-by-Codon Modulation of Translational Speed and Accuracy Via mRNA Folding
title_fullStr Codon-by-Codon Modulation of Translational Speed and Accuracy Via mRNA Folding
title_full_unstemmed Codon-by-Codon Modulation of Translational Speed and Accuracy Via mRNA Folding
title_short Codon-by-Codon Modulation of Translational Speed and Accuracy Via mRNA Folding
title_sort codon-by-codon modulation of translational speed and accuracy via mrna folding
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106722/
https://www.ncbi.nlm.nih.gov/pubmed/25051069
http://dx.doi.org/10.1371/journal.pbio.1001910
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