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Tomaz da Silva P, Zhang Y, Theodorakis E, Martens LD, Yépez VA, Pelechano V, Gagneur J
Mol Syst Biol 20 (5) 506-520 [2024-05-00; online 2024-03-15]
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.
PubMed 38491213
DOI 10.1038/s44320-024-00026-9
Crossref 10.1038/s44320-024-00026-9
pmc: PMC11066088
pii: 10.1038/s44320-024-00026-9