Cellular energy regulates mRNA degradation in a codon-specific manner

Pedro Tomaz da Silva, Yujie Zhang, Evangelos Theodorakis, Laura D. Martens, Vicente A. Yépez, Vicent Pelechano, Julien Gagneur

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)506-520
Number of pages15
JournalMolecular Systems Biology
Volume20
Issue number5
DOIs
StatePublished - 2 May 2024

Keywords

  • mRNA Stability; Cellular Energy Metabolism; Tissue-specific Regulation; Codon Usage Bias; Codon Optimality-mediated mRNA Degradation

Fingerprint

Dive into the research topics of 'Cellular energy regulates mRNA degradation in a codon-specific manner'. Together they form a unique fingerprint.

Cite this