m6A RNA methylation: from mechanisms to therapeutic potential

RNA carries a diverse array of chemical modifications that play important roles in the regulation of gene expression. N 6 ‐methyladenosine (m 6 A), installed onto mRNA by the METTL3/METTL14 methyltransferase complex, is the most prevalent mRNA modification. m 6 A methylation regulates gene expressio...

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Veröffentlicht in:The EMBO journal Jg. 40; H. 3
Hauptverfasser: He, P Cody, He, Chuan
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 01.02.2021
Springer Nature B.V
John Wiley and Sons Inc
Schlagworte:
Decay
DNA methylation
EMBO36
epitranscriptome
Gene expression
Gene regulation
m6A methylation
Methylation
Methyltransferase
mRNA
mRNA processing
mRNA turnover
N6-methyladenosine
Nuclear transport
Review
Reviews
Ribonucleic acid
RNA
RNA modification
RNA modifications
Substrates
Transcription
Translation
epitranscriptome
mRNA
m
A methylation
gene expression
RNA modifications
ISSN:0261-4189, 1460-2075
Online-Zugang:Volltext
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Zusammenfassung:RNA carries a diverse array of chemical modifications that play important roles in the regulation of gene expression. N 6 ‐methyladenosine (m 6 A), installed onto mRNA by the METTL3/METTL14 methyltransferase complex, is the most prevalent mRNA modification. m 6 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 6 A methylation as a mode of post‐transcriptional gene expression regulation is evident in the crucial roles m 6 A‐mediated gene regulation plays in numerous physiological and pathophysiological processes. Here, we review current knowledge on the mechanisms by which m 6 A exerts its functions and discuss recent advances that underscore the multifaceted role of m 6 A in the regulation of gene expression. We highlight advances in our understanding of the regulation of m 6 A deposition on mRNA and its context‐dependent effects on mRNA decay and translation, the role of m 6 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 6 A regulators in disease. Graphical Abstract Roles of the most prevalent RNA modification in post‐transcriptional regulation of gene expression, the latest understanding of its deposition and removal, and the possibility of its targeting in disease are discussed in this comprehensive review.
Bibliographie:ObjectType-Article-1
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ISSN:0261-4189
1460-2075
DOI:10.15252/embj.2020105977