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Codon optimality, bias and usage in translation and mRNA decay
Nature Reviews Molecular Cell Biology ( IF 112.7 ) Pub Date :  , DOI: 10.1038/nrm.2017.91
Gavin Hanson , Jeff Coller

The advent of ribosome profiling and other tools to probe mRNA translation has revealed that codon bias — the uneven use of synonymous codons in the transcriptome — serves as a secondary genetic code: a code that guides the efficiency of protein production, the fidelity of translation and the metabolism of mRNAs. Recent advancements in our understanding of mRNA decay have revealed a tight coupling between ribosome dynamics and the stability of mRNA transcripts; this coupling integrates codon bias into the concept of codon optimality, or the effects that specific codons and tRNA concentrations have on the efficiency and fidelity of the translation machinery. In this Review, we first discuss the evidence for codon-dependent effects on translation, beginning with the basic mechanisms through which translation perturbation can affect translation efficiency, protein folding and transcript stability. We then discuss how codon effects are leveraged by the cell to tailor the proteome to maintain homeostasis, execute specific gene expression programmes of growth or differentiation and optimize the efficiency of protein production.

中文翻译:

密码子的最佳性,偏倚以及翻译和mRNA衰减中的用法

核糖体图谱分析和其他可探测mRNA翻译的工具的出现表明,密码子偏倚(转录组中同义密码子的使用不均)可作为辅助遗传密码:指导蛋白质生产效率,翻译保真度和编码效率的密码。 mRNA的代谢。我们对mRNA衰变的了解的最新进展表明,核糖体动力学与mRNA转录物的稳定性之间存在紧密的联系。这种耦合将密码子偏倚整合到密码子最佳化的概念中,或者将特定密码子和tRNA浓度对翻译机制的效率和保真度产生影响。在这篇评论中,我们首先讨论了依赖密码子对翻译的影响的证据,首先从翻译干扰可影响翻译效率,蛋白质折叠和转录本稳定性的基本机制入手。然后,我们讨论细胞如何利用密码子效应来定制蛋白质组以维持体内稳态,执行生长或分化的特定基因表达程序并优化蛋白质生产的效率。
更新日期:2017-10-11
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