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Tomaz da Silva, P.* ; Zhang, Y.* ; Theodorakis, E.* ; Martens, L.D. ; Yépez, V.A.* ; Pelechano, V.* ; Gagneur, J.

Cellular energy regulates mRNA degradation in a codon-specific manner.

Mol. Syst. Biol. 20, 506-520 (2024)
DOI PMC
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Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.
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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Mrna Stability; Cellular Energy Metabolism; Tissue-specific Regulation; Codon Usage Bias; Codon Optimality-mediated Mrna Degradation; Gene-expression; Optimality; Translation; Reveals; Quantification; Elongation; Principles; Mechanism; Dynamics; Database
ISSN (print) / ISBN 1744-4292
e-ISSN 1744-4292
Journal Molecular Systems Biology
Quellenangaben Volume: 20, Issue: 5, Pages: 506-520 Article Number: , Supplement: ,
Publisher EMBO Press
Publishing Place Campus, 4 Crinan St, London, N1 9xw, England
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
Grants National Institute of Neurological Disorders and Stroke
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)
German Bundesministerium fr Bildung und Forschung (BMBF) through the Model Exchange for Regulatory Genomics project MERGE
Helmholtz Association under the joint research school Munich School for Data Science - Munich Center for Machine Learning (MCML)
Swedish Research Council
Wallenberg Academy Fellowship
Swedish Foundations' Starting Grant (Ragnar Sderberg Foundation)
Vinnova
Karolinska Institutet (SciLifeLab Fellowship)
SFO and KI funds - China Scholarship Council
Common Fund of the Office of the Director of the National Institutes of Health
National Cancer Institute, National Human Genome Research Institute, National Heart, Lung, and Blood Institute, National Institute on Drug Abuse, National Institute of Mental Health
Deutsche Forschungsgemeinschaft (DFG)