The Crosstalk Between Metabolism and Translation

Overview

Journal Cell Metab

Publisher Cell Press

Specialties Cell Biology
Endocrinology

Date 2024 Sep 4

PMID 39232280

Authors

Stefano Biffo

Davide Ruggero

Massimo Mattia Santoro

Affiliations

Soon will be listed here.

Abstract

Metabolism and mRNA translation represent critical steps involved in modulating gene expression and cellular physiology. Being the most energy-consuming process in the cell, mRNA translation is strictly linked to cellular metabolism and in synchrony with it. Indeed, several mRNAs for metabolic pathways are regulated at the translational level, resulting in translation being a coordinator of metabolism. On the other hand, there is a growing appreciation for how metabolism impacts several aspects of RNA biology. For example, metabolic pathways and metabolites directly control the selectivity and efficiency of the translational machinery, as well as post-transcriptional modifications of RNA to fine-tune protein synthesis. Consistently, alterations in the intricate interplay between translational control and cellular metabolism have emerged as a critical axis underlying human diseases. A better understanding of such events will foresee innovative therapeutic strategies in human disease states.

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References

Kim S, Choi J, Marsal-Garcia L, Amiri M, Yanagiya A, Sonenberg N . The mRNA translation initiation factor eIF4G1 controls mitochondrial oxidative phosphorylation, axonal morphogenesis, and memory. Proc Natl Acad Sci U S A. 2023; 120(25):e2300008120. PMC: 10288579. DOI: 10.1073/pnas.2300008120. View

Yang H, Zingaro V, Lincoff J, Tom H, Oikawa S, Oses-Prieto J . Remodelling of the translatome controls diet and its impact on tumorigenesis. Nature. 2024; 633(8028):189-197. DOI: 10.1038/s41586-024-07781-7. View

Shetty S, Varshney U . Regulation of translation by one-carbon metabolism in bacteria and eukaryotic organelles. J Biol Chem. 2020; 296:100088. PMC: 7949028. DOI: 10.1074/jbc.REV120.011985. View

Buccitelli C, Selbach M . mRNAs, proteins and the emerging principles of gene expression control. Nat Rev Genet. 2020; 21(10):630-644. DOI: 10.1038/s41576-020-0258-4. View

Missiaen R, Anderson N, Kim L, Nance B, Burrows M, Skuli N . GCN2 inhibition sensitizes arginine-deprived hepatocellular carcinoma cells to senolytic treatment. Cell Metab. 2022; 34(8):1151-1167.e7. PMC: 9357184. DOI: 10.1016/j.cmet.2022.06.010. View

Samuel V, Shulman G . Nonalcoholic Fatty Liver Disease as a Nexus of Metabolic and Hepatic Diseases. Cell Metab. 2017; 27(1):22-41. PMC: 5762395. DOI: 10.1016/j.cmet.2017.08.002. View

Sonenberg N, Trachsel H, Hecht S, Shatkin A . Differential stimulation of capped mRNA translation in vitro by cap binding protein. Nature. 1980; 285(5763):331-3. DOI: 10.1038/285331a0. View

Yoshizawa T, Hinoi E, Jung D, Kajimura D, Ferron M, Seo J . The transcription factor ATF4 regulates glucose metabolism in mice through its expression in osteoblasts. J Clin Invest. 2009; 119(9):2807-17. PMC: 2735903. DOI: 10.1172/JCI39366. View

Sinvani H, Haimov O, Svitkin Y, Sonenberg N, Tamarkin-Ben-Harush A, Viollet B . Translational tolerance of mitochondrial genes to metabolic energy stress involves TISU and eIF1-eIF4GI cooperation in start codon selection. Cell Metab. 2015; 21(3):479-92. DOI: 10.1016/j.cmet.2015.02.010. View

10.

Renz P, Valdivia-Francia F, Sendoel A . Some like it translated: small ORFs in the 5'UTR. Exp Cell Res. 2020; 396(1):112229. DOI: 10.1016/j.yexcr.2020.112229. View

11.

Both G, Furuichi Y, Muthukrishnan S, Shatkin A . Ribosome binding to reovirus mRNA in protein synthesis requires 5' terminal 7-methylguanosine. Cell. 1975; 6(2):185-95. DOI: 10.1016/0092-8674(75)90009-4. View

12.

Ceci M, Gaviraghi C, Gorrini C, Sala L, Offenhauser N, Marchisio P . Release of eIF6 (p27BBP) from the 60S subunit allows 80S ribosome assembly. Nature. 2003; 426(6966):579-84. DOI: 10.1038/nature02160. View

13.

Shahbazian D, Parsyan A, Petroulakis E, Topisirovic I, Martineau Y, Gibbs B . Control of cell survival and proliferation by mammalian eukaryotic initiation factor 4B. Mol Cell Biol. 2010; 30(6):1478-85. PMC: 2832492. DOI: 10.1128/MCB.01218-09. View

14.

Meyuhas O, Dreazen A . Ribosomal protein S6 kinase from TOP mRNAs to cell size. Prog Mol Biol Transl Sci. 2010; 90:109-53. DOI: 10.1016/S1877-1173(09)90003-5. View

15.

Basu A, Poddar D, Robinet P, Smith J, Febbraio M, Baldwin 3rd W . Ribosomal protein L13a deficiency in macrophages promotes atherosclerosis by limiting translation control-dependent retardation of inflammation. Arterioscler Thromb Vasc Biol. 2014; 34(3):533-42. PMC: 3954853. DOI: 10.1161/ATVBAHA.113.302573. View

16.

Zhu J, Thompson C . Metabolic regulation of cell growth and proliferation. Nat Rev Mol Cell Biol. 2019; 20(7):436-450. PMC: 6592760. DOI: 10.1038/s41580-019-0123-5. View

17.

Mahe M, Rios-Fuller T, Katsara O, Schneider R . Non-canonical mRNA translation initiation in cell stress and cancer. NAR Cancer. 2024; 6(2):zcae026. PMC: 11140632. DOI: 10.1093/narcan/zcae026. View

18.

Yamada T, Ishihara H, Tamura A, Takahashi R, Yamaguchi S, Takei D . WFS1-deficiency increases endoplasmic reticulum stress, impairs cell cycle progression and triggers the apoptotic pathway specifically in pancreatic beta-cells. Hum Mol Genet. 2006; 15(10):1600-9. DOI: 10.1093/hmg/ddl081. View

19.

Gandin V, Miluzio A, Barbieri A, Beugnet A, Kiyokawa H, Marchisio P . Eukaryotic initiation factor 6 is rate-limiting in translation, growth and transformation. Nature. 2008; 455(7213):684-8. PMC: 2753212. DOI: 10.1038/nature07267. View

20.

Larsson O, Morita M, Topisirovic I, Alain T, Blouin M, Pollak M . Distinct perturbation of the translatome by the antidiabetic drug metformin. Proc Natl Acad Sci U S A. 2012; 109(23):8977-82. PMC: 3384216. DOI: 10.1073/pnas.1201689109. View