Codon-by-codon modulation of translational speed and accuracy via mRNA folding

PLoS Biology
Jian-Rong YangJianzhi Zhang


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.


May 20, 1989·Journal of Molecular Biology·M A SørensenS Pedersen
Mar 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·A C ChangS N Cohen
Jul 22, 1997·Proceedings of the National Academy of Sciences of the United States of America·J R Powell, E N Moriyama
Nov 19, 1997·Molecular Biology and Evolution·X Gu, J Zhang
Nov 5, 1999·Trends in Biochemical Sciences·J R Warner
Sep 11, 2002·Progress in Nucleic Acid Research and Molecular Biology·Gaël Cristofari, Jean-Luc Darlix
Nov 16, 2002·Current Opinion in Genetics & Development·Laurent Duret
Mar 1, 1965·Journal of Molecular Biology·M REVEL, H H HIATT
Oct 17, 2003·Nature·Sina GhaemmaghamiJonathan S Weissman
Mar 11, 2005·Molecular Biology and Evolution·Andreas Wagner
Aug 19, 2006·Proceedings of the National Academy of Sciences of the United States of America·Archana BelleErin K O'Shea
Nov 15, 2006·Molecular Biology and Evolution·Nina Stoletzki, Adam Eyre-Walker
May 8, 2007·Molecular Biology and Evolution·Ziheng Yang
Jul 25, 2007·Bioinformatics·Ilan WapinskiAviv Regev
Sep 12, 2007·Bioinformatics·M A LarkinD G Higgins
Mar 11, 2008·Nature·Jin-Der WenIgnacio Tinoco
Sep 30, 2008·Journal of Molecular Biology·Jianli Lu, Carol Deutsch
Nov 6, 2008·Annual Review of Genetics·Ruth Hershberg, Dmitri A Petrov
Feb 10, 2009·Nature Structural & Molecular Biology·Gong ZhangZoya Ignatova
Feb 26, 2009·Cell·Hani S Zaher, Rachel Green
Apr 11, 2009·Science·Grzegorz KudlaJoshua B Plotkin
Mar 20, 2010·Annual Review of Biochemistry·Joachim Frank, Ruben L Gonzalez
Mar 24, 2010·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Paul M SharpKai Zeng
May 21, 2010·PLoS Genetics·Jean-François GoutUNKNOWN Paramecium Post-Genomics Consortium
Sep 3, 2010·Nature·Michael KerteszEran Segal
Oct 5, 2010·Genome Biology and Evolution·Joshua L Cherry
Oct 21, 2010·Molecular Systems Biology·Jian-Rong YangJianzhi Zhang
Nov 27, 2010·Science·Adam Ben-ShemMarat Yusupov
Dec 29, 2010·Proceedings of the National Academy of Sciences of the United States of America·Kerry A Geiler-SamerotteD Allan Drummond
Nov 3, 2011·RNA·Michael Stadler, Andrew Fire
Nov 5, 2011·Genome Biology·Tamir TullerMichal Ziv-Ukelson
Nov 17, 2011·Nucleic Acids Research·Paul FlicekStephen M J Searle
Nov 24, 2011·Nucleic Acids Research·J Michael CherryEdith D Wong
Dec 23, 2011·Proceedings of the National Academy of Sciences of the United States of America·Magnus JohanssonMåns Ehrenberg
Dec 24, 2011·Science·Gloria A BrarJonathan S Weissman
Jan 17, 2012·Advances in Protein Chemistry and Structural Biology·Marina V Rodnina

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