Ageing is a conserved and unavoidable biological process characterized by progressive decline of physiological functions with time. Despite constituting the greatest risk factor for most human diseases, little is known about the molecular mechanisms driving the ageing process. More than 170 chemical RNA modifications, also known as the epitranscriptome, decorate eukaryotic coding and non-coding RNAs and have emerged as novel regulators of RNA metabolism, modulating RNA stability, translation, splicing or non-coding RNA processing. Studies on short-lived organisms such as yeast or worms connect mutations on RNA modifying enzymes with lifespan changes, and dysregulation of the epitranscriptome has been linked to age-related diseases and ageing hallmarks themselves in mammals. Moreover, transcriptome-wide analyses are starting to reveal changes in messenger RNA modifications in neurodegenerative diseases and in the expression of some RNA modifiers with age. These studies are starting to put the focus on the epitranscriptome as a potential novel regulator of ageing and lifespan, and open new avenues for the identification of targets to treat age-related diseases. In this review, we discuss the connection between RNA modifications and the enzymatic machinery regulating their deposition in coding and non-coding RNAs, and ageing and hypothesize about the potential role of RNA modifications in the regulation of other ncRNAs playing a key role in ageing, such as transposable elements and tRNA fragments. Finally, we reanalyze available datasets of mouse tissues during ageing and report a wide transcriptional dysregulation of proteins involved in the deposition, removal or decoding of several of the best-known RNA modifications.
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April 2023
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The cover of this edition of Biochemical Society Transactions features a super-resolution image of mouse heart mitochondria. Shammas, Huang and Narendra discuss the present understanding of neurodegeneration and myopathy caused by mutations in the mitochondrial proteins CHCHD2 and CHCHD10, and putting forth potential therapeutic strategies to combat these diseases in ‘CHCHD2 and CHCHD10-related neurodegeneration: molecular pathogenesis and the path to precision therapy’ on pp 797-809.
Review Article|
April 04 2023
Epitranscriptomics: new players in an old game
Alba Coego;
Alba Coego
*
Epitranscriptomics and Ageing Group. Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela (USC), Santiago de Compostela 15782, Spain
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Helena Covelo-Molares;
Helena Covelo-Molares
*
Epitranscriptomics and Ageing Group. Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela (USC), Santiago de Compostela 15782, Spain
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Diana Guallar
Epitranscriptomics and Ageing Group. Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela (USC), Santiago de Compostela 15782, Spain
Correspondence: Diana Guallar (diana.guallar@usc.es)
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Publisher: Portland Press Ltd
Received:
February 03 2023
Revision Received:
March 17 2023
Accepted:
March 20 2023
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2023 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2023
Biochem Soc Trans (2023) 51 (2): 783–796.
Article history
Received:
February 03 2023
Revision Received:
March 17 2023
Accepted:
March 20 2023
Citation
Alba Coego, Helena Covelo-Molares, Diana Guallar; Epitranscriptomics: new players in an old game. Biochem Soc Trans 26 April 2023; 51 (2): 783–796. doi: https://doi.org/10.1042/BST20221417
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