Ribosomes modulate transcriptome abundance via generalized frameshift and out-of-frame mRNA decay

IF 14.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cell Pub Date : 2025-05-15 DOI:10.1016/j.molcel.2025.04.022

Yujie Zhang, Lilit Nersisyan, Eliska Fürst, Ioannis Alexopoulos, Carlos Santolaria, Susanne Huch, Claudio Bassot, Elena Garre, Per Sunnerhagen, Ilaria Piazza, Vicent Pelechano

{"title":"Ribosomes modulate transcriptome abundance via generalized frameshift and out-of-frame mRNA decay","authors":"Yujie Zhang, Lilit Nersisyan, Eliska Fürst, Ioannis Alexopoulos, Carlos Santolaria, Susanne Huch, Claudio Bassot, Elena Garre, Per Sunnerhagen, Ilaria Piazza, Vicent Pelechano","doi":"10.1016/j.molcel.2025.04.022","DOIUrl":null,"url":null,"abstract":"Cells need to adapt their transcriptome to quickly match cellular needs in changing environments. mRNA abundance can be controlled by altering both its synthesis and decay. Here, we show how, in response to poor nutritional conditions, the bulk of the <em>S. cerevisiae</em> transcriptome undergoes −1 ribosome frameshifts and experiences an accelerated out-of-frame co-translational mRNA decay. Using RNA metabolic labeling, we demonstrate that in poor nutritional conditions, nonsense-mediated mRNA decay (NMD)-dependent degradation represents at least one-third of the total mRNA decay. We further characterize this mechanism and identify low codon optimality as a key factor for ribosomes to induce out-of-frame mRNA decay. Finally, we show that this phenomenon is conserved from bacteria to humans. Our work provides evidence for a direct regulatory feedback mechanism coupling protein demand with the control of mRNA abundance to limit cellular growth and broadens the functional landscape of mRNA quality control.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"141 1","pages":""},"PeriodicalIF":14.5000,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Cell","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.molcel.2025.04.022","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Cells need to adapt their transcriptome to quickly match cellular needs in changing environments. mRNA abundance can be controlled by altering both its synthesis and decay. Here, we show how, in response to poor nutritional conditions, the bulk of the S. cerevisiae transcriptome undergoes −1 ribosome frameshifts and experiences an accelerated out-of-frame co-translational mRNA decay. Using RNA metabolic labeling, we demonstrate that in poor nutritional conditions, nonsense-mediated mRNA decay (NMD)-dependent degradation represents at least one-third of the total mRNA decay. We further characterize this mechanism and identify low codon optimality as a key factor for ribosomes to induce out-of-frame mRNA decay. Finally, we show that this phenomenon is conserved from bacteria to humans. Our work provides evidence for a direct regulatory feedback mechanism coupling protein demand with the control of mRNA abundance to limit cellular growth and broadens the functional landscape of mRNA quality control.

Abstract Image

查看原文本刊更多论文

核糖体通过广义移码和框外mRNA衰变调节转录组丰度

细胞需要调整它们的转录组，以便在不断变化的环境中快速匹配细胞的需要。mRNA丰度可以通过改变其合成和衰变来控制。在这里，我们展示了在不良营养条件下，酿酒葡萄球菌的大部分转录组如何经历- 1核糖体帧移，并经历加速的帧外共翻译mRNA衰变。利用RNA代谢标记，我们证明在营养不良的条件下，无义介导的mRNA衰变（NMD）依赖的降解至少占总mRNA衰变的三分之一。我们进一步表征了这一机制，并确定低密码子最优性是核糖体诱导框外mRNA衰变的关键因素。最后，我们表明这种现象从细菌到人类都是保守的。我们的工作为直接调节反馈机制提供了证据，该机制将蛋白质需求与mRNA丰度的控制结合起来，以限制细胞生长，并拓宽了mRNA质量控制的功能领域。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Molecular Cell 生物-生化与分子生物学

CiteScore

26.00

自引率

3.80%

发文量

389

审稿时长

1 months

期刊介绍： Molecular Cell is a companion to Cell, the leading journal of biology and the highest-impact journal in the world. Launched in December 1997 and published monthly. Molecular Cell is dedicated to publishing cutting-edge research in molecular biology, focusing on fundamental cellular processes. The journal encompasses a wide range of topics, including DNA replication, recombination, and repair; Chromatin biology and genome organization; Transcription; RNA processing and decay; Non-coding RNA function; Translation; Protein folding, modification, and quality control; Signal transduction pathways; Cell cycle and checkpoints; Cell death; Autophagy; Metabolism.