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

PLoS Biology
Jian-Rong YangJianzhi Zhang

Abstract

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.

References

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

❮ Previous
Next ❯

Citations

Nov 25, 2014·Nature Structural & Molecular Biology·Sebastian PechmannJudith Frydman
Oct 22, 2015·Molecular Biology and Evolution·Zhenguo Zhang, Daven C Presgraves
May 29, 2015·Bioinformatics·Wenlong ShenZhihu Zhao
Dec 17, 2014·Ecology and Evolution·Michael D Kessler, Matthew D Dean
Jun 4, 2015·Current Opinion in Structural Biology·Roslyn M Bill, Tobias von der Haar
Jul 15, 2015·BMC Genomics·Daniel López, Florencio Pazos
Jun 6, 2015·Cell·Vicent PelechanoLars M Steinmetz
Jun 10, 2015·Nature Reviews. Genetics·Jianzhi Zhang, Jian-Rong Yang
Dec 8, 2015·PloS One·Xiaojuan ShenGuanglin Li
Sep 24, 2016·Quarterly Reviews of Biophysics·Jin ChenJoseph D Puglisi
Nov 11, 2015·Scientific Reports·Naoko AbeHiroshi Abe
Apr 1, 2017·Current Opinion in Genetics & Development·Cédric Gobet, Felix Naef
Dec 10, 2016·Haemophilia : the Official Journal of the World Federation of Hemophilia·N Hamasaki-KatagiriC Kimchi-Sarfaty
Jan 2, 2015·Genome Biology and Evolution·Xinzhu Wei, Jianzhi Zhang
Mar 15, 2015·Nucleic Acids Research·Thomas E GorochowskiJohannes A Roubos
Dec 17, 2014·Nucleic Acids Research·Tamir Tuller, Hadas Zur
May 13, 2015·PloS One·Anne-Katrin HessZoya Ignatova
Oct 5, 2016·Nature Communications·Patrick B F O'ConnorPavel V Baranov
Jun 18, 2016·Science·Tatsuya MorisakiTimothy J Stasevich
Dec 28, 2019·RNA·Anthony Khong, Roy Parker
Mar 11, 2016·The Journal of Biological Chemistry·Seung-Wook HaYouming Xie
Dec 30, 2014·Molecular Biology and Evolution·Jian-Rong Yang, Jianzhi Zhang
Nov 1, 2016·Genome Biology and Evolution·Kevin N ChesmoreScott M Williams
Oct 11, 2017·DNA Research : an International Journal for Rapid Publication of Reports on Genes and Genomes·Meng-Ze DuFeng-Biao Guo
Apr 17, 2020·Proceedings of the National Academy of Sciences of the United States of America·Cédric GobetFelix Naef
Jul 31, 2018·Genome Biology and Evolution·Xinzhu Wei, Jianzhi Zhang
Aug 18, 2020·Molecular Biology and Evolution·Zhengting Zou, Jianzhi Zhang
Dec 22, 2020·Molecular Biology and Evolution·Mengyi Sun, Jianzhi Zhang
Nov 1, 2020·Cellular and Molecular Life Sciences : CMLS·Fabian Hia, Osamu Takeuchi
Feb 5, 2021·The FEBS Journal·Pedro do Couto Bordignon, Sebastian Pechmann
Feb 20, 2021·Genomics, Proteomics & Bioinformatics·Gongwang YuJian-Rong Yang

❮ Previous
Next ❯

Methods Mentioned

BETA
protein folding

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Hereditary Sensory Autonomic Neuropathy

Hereditary Sensory Autonomic Neuropathies are a group of inherited neurodegenerative disorders characterized clinically by loss of sensation and autonomic dysfunction. Here is the latest research on these neuropathies.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Landau-Kleffner Syndrome

Landau Kleffner syndrome (LKS), also called infantile acquired aphasia, acquired epileptic aphasia, or aphasia with convulsive disorder, is a rare childhood neurological syndrome characterized by the sudden or gradual development of aphasia (the inability to understand or express language) and an abnormal electroencephalogram. Discover the latest research on LKS here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Regulation of Vocal-Motor Plasticity

Dopaminergic projections to the basal ganglia and nucleus accumbens shape the learning and plasticity of motivated behaviors across species including the regulation of vocal-motor plasticity and performance in songbirds. Discover the latest research on the regulation of vocal-motor plasticity here.