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M A RNA Methylation: from Mechanisms to Therapeutic Potential

Overview
Journal EMBO J
Date 2021 Jan 20
PMID 33470439
Citations 291
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Abstract

RNA carries a diverse array of chemical modifications that play important roles in the regulation of gene expression. N -methyladenosine (m A), installed onto mRNA by the METTL3/METTL14 methyltransferase complex, is the most prevalent mRNA modification. m A methylation regulates gene expression by influencing numerous aspects of mRNA metabolism, including pre-mRNA processing, nuclear export, decay, and translation. The importance of m A methylation as a mode of post-transcriptional gene expression regulation is evident in the crucial roles m A-mediated gene regulation plays in numerous physiological and pathophysiological processes. Here, we review current knowledge on the mechanisms by which m A exerts its functions and discuss recent advances that underscore the multifaceted role of m A in the regulation of gene expression. We highlight advances in our understanding of the regulation of m A deposition on mRNA and its context-dependent effects on mRNA decay and translation, the role of m A methylation of non-coding chromosomal-associated RNA species in regulating transcription, and the activities of the RNA demethylase FTO on diverse substrates. We also discuss emerging evidence for the therapeutic potential of targeting m A regulators in disease.

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