Cellular Energy Regulates MRNA Degradation in a Codon-specific Manner

Overview

Journal Mol Syst Biol

Specialty Molecular Biology

Date 2024 Mar 16

PMID 38491213

Authors

Pedro Tomaz da Silva

Yujie Zhang

Evangelos Theodorakis

Laura D Martens

Vicente A Yepez

Vicent Pelechano

Julien Gagneur

Affiliations

Soon will be listed here.

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.

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