Abstract
While epigenetic modifications of DNA and histones play main roles in gene transcription regulation, recently discovered post-transcriptional RNA modifications, known as epitranscriptomic modifications, have been found to have a profound impact on gene expression by regulating RNA stability, localization and decoding efficiency. Importantly, genetic variations or environmental perturbations of epitranscriptome modifiers (that is, writers, erasers and readers) are associated with obesity and metabolic diseases, such as type 2 diabetes. The epitranscriptome is closely coupled to epigenetic signalling, adding complexity to our understanding of gene expression in both health and disease. Moreover, the epitranscriptome in the parental generation can affect organismal phenotypes in the next generation. In this Review, we discuss the relationship between epitranscriptomic modifications and metabolic diseases, their relationship with the epigenome and possible therapeutic strategies.
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Acknowledgements
We thank the members of the Sakai laboratories, Tohoku University Graduate School of Medicine (Sendai, Japan), and the Research Centre for Advanced Science and Technology, The University of Tokyo (Tokyo, Japan) for their helpful discussions. This study was supported by grants-in-aid for scientific research (JP21H04826 to J.S., JP21H02659 to F.-Y.W., JP22K06178 to Y.M.), for exploratory research (JP20K21747 to J.S.), for pioneering research (JP22K18411 to J.S.) from the Ministry of Education, Science, Sports and Culture (MEXT), AMED-CREST (JP20gm1310007 to Y.M. and J.S.) FOREST (JPMJFR205Y to F.-Y.W.) from the Japan Science and Technology Agency (JST) and the Takeda Science Foundation (to Y.M.).
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Y.M., F.-Y.W. and J.S. conceived the concepts described in this Review. Y.M., F.-Y.W. and J.S. wrote the manuscript. Figures were prepared by Y.M. and F.-Y.W.
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Matsumura, Y., Wei, FY. & Sakai, J. Epitranscriptomics in metabolic disease. Nat Metab 5, 370–384 (2023). https://doi.org/10.1038/s42255-023-00764-4
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DOI: https://doi.org/10.1038/s42255-023-00764-4
