Cellular energy regulates mRNA degradation in a codon-specific manner.
Mol Syst Biol
; 20(5): 506-520, 2024 May.
Article
em En
| MEDLINE
| ID: mdl-38491213
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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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Códon
/
RNA Mensageiro
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Estabilidade de RNA
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Metabolismo Energético
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article