title: Codon-by-codon modulation of translational speed and accuracy via mRNA folding.
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.
authors: Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Jian-Rong
authors: JR
authors: Yang
authors: Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Xiaoshu
authors: X
authors: Chen
authors: Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Jianzhi
authors: J
authors: Zhang
mesh_terms: D000818:Animals; D003062:Codon; D053595:Embryonic Stem Cells / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D051379:Mice; D008954:Models, Biological; D010441:Peptide Chain Elongation, Translational / Q000502:physiology*; D059370:RNA Folding / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism
chemical_list: D003062:Codon; D012333:RNA, Messenger