Cellular energy regulates mRNA degradation in a codon-specific manner.

IF 8.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Molecular Systems Biology Pub Date : 2024-05-01 Epub Date: 2024-03-15 DOI:10.1038/s44320-024-00026-9
Pedro Tomaz da Silva, Yujie Zhang, Evangelos Theodorakis, Laura D Martens, Vicente A Yépez, Vicent Pelechano, Julien Gagneur
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引用次数: 0

Abstract

Codon optimality is a major determinant of mRNA translation and degradation rates. However, whether and through which mechanisms its effects are regulated remains poorly understood. Here we show that codon optimality associates with up to 2-fold change in mRNA stability variations between human tissues, and that its effect is attenuated in tissues with high energy metabolism and amplifies with age. Mathematical modeling and perturbation data through oxygen deprivation and ATP synthesis inhibition reveal that cellular energy variations non-uniformly alter the effect of codon usage. This new mode of codon effect regulation, independent of tRNA regulation, provides a fundamental mechanistic link between cellular energy metabolism and eukaryotic gene expression.

细胞能量以密码子特异性方式调节 mRNA 降解。
密码子优化是 mRNA 翻译和降解率的主要决定因素。然而,人们对其影响是否受到调控以及通过何种机制调控仍然知之甚少。在这里,我们发现密码子优化与不同人体组织之间 mRNA 稳定性的变化有关,变化幅度可达 2 倍,其影响在高能量代谢的组织中减弱,并随着年龄的增长而增强。通过缺氧和抑制 ATP 合成的数学建模和扰动数据显示,细胞能量变化会不均匀地改变密码子使用的效果。这种独立于 tRNA 调节的新的密码子效应调节模式,为细胞能量代谢和真核生物基因表达之间提供了基本的机理联系。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Molecular Systems Biology
Molecular Systems Biology 生物-生化与分子生物学
CiteScore
18.50
自引率
1.00%
发文量
62
审稿时长
6-12 weeks
期刊介绍: Systems biology is a field that aims to understand complex biological systems by studying their components and how they interact. It is an integrative discipline that seeks to explain the properties and behavior of these systems. Molecular Systems Biology is a scholarly journal that publishes top-notch research in the areas of systems biology, synthetic biology, and systems medicine. It is an open access journal, meaning that its content is freely available to readers, and it is peer-reviewed to ensure the quality of the published work.
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