Codon bias confers stability to human mRNAs
Codon bias confers stability to human mRNAs
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DOI：
10.15252/embr.201948220
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发表时间：
2019-11-05
期刊：
影响因子：
7.7
通讯作者：
Takeuchi, Osamu
中科院分区：
文献类型：
--
作者：
Hia, Fabian;Yang, Sheng Fan;Takeuchi, Osamu
密码子偏好性是影响几种模式生物mRNA稳定性的主要因素之一。然而，密码子偏好性对mRNA稳定性的分子机制在人类中仍不清楚。在这里，我们表明，人类细胞具有通过独特的密码子偏好调节RNA稳定性的机制。生物信息学分析表明，密码子可分为两类：第三位碱基为G或C的密码子（GC 3）和第三位碱基为A或T的密码子（AT 3），前者稳定mRNA，后者使mRNA失稳。密码子偏好性的定量显示，GC 3含量增加导致GC含量成比例地更高。通过生物信息学，核糖体分析，并在体外分析，我们表明，解耦的密码子偏好的影响揭示了两种模式的mRNA调控，一个GC 3和GC含量依赖。采用免疫沉淀为基础的策略，我们确定ILF2和ILF3作为RNA结合蛋白，差异调节全球mRNA丰度的基础上的密码子偏好。我们的研究结果表明，密码子偏好是一个双管齐下的系统，管理mRNA丰度。
Codon bias has been implicated as one of the major factors contributing to mRNA stability in several model organisms. However, the molecular mechanisms of codon bias on mRNA stability remain unclear in humans. Here, we show that human cells possess a mechanism to modulate RNA stability through a unique codon bias. Bioinformatics analysis showed that codons could be clustered into two distinct groups-codons with G or C at the third base position (GC3) and codons with either A or T at the third base position (AT3): the former stabilizing while the latter destabilizing mRNA. Quantification of codon bias showed that increased GC3-content entails proportionately higher GC-content. Through bioinformatics, ribosome profiling, and in vitro analysis, we show that decoupling the effects of codon bias reveals two modes of mRNA regulation, one GC3- and one GC-content dependent. Employing an immunoprecipitation-based strategy, we identify ILF2 and ILF3 as RNA-binding proteins that differentially regulate global mRNA abundances based on codon bias. Our results demonstrate that codon bias is a two-pronged system that governs mRNA abundance.