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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Vydané v:The EMBO journal Ročník 40; číslo 3
Hlavní autori: He, P Cody, He, Chuan
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: London Nature Publishing Group UK 01.02.2021
Springer Nature B.V
John Wiley and Sons Inc
Predmet:
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
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Abstract 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.
AbstractList RNA carries a diverse array of chemical modifications that play important roles in the regulation of gene expression. N6‐methyladenosine (m6A), installed onto mRNA by the METTL3/METTL14 methyltransferase complex, is the most prevalent mRNA modification. m6A methylation regulates gene expression by influencing numerous aspects of mRNA metabolism, including pre‐mRNA processing, nuclear export, decay, and translation. The importance of m6A methylation as a mode of post‐transcriptional gene expression regulation is evident in the crucial roles m6A‐mediated gene regulation plays in numerous physiological and pathophysiological processes. Here, we review current knowledge on the mechanisms by which m6A exerts its functions and discuss recent advances that underscore the multifaceted role of m6A in the regulation of gene expression. We highlight advances in our understanding of the regulation of m6A deposition on mRNA and its context‐dependent effects on mRNA decay and translation, the role of m6A 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 m6A regulators in disease.
RNA carries a diverse array of chemical modifications that play important roles in the regulation of gene expression. N 6‐methyladenosine (m6A), installed onto mRNA by the METTL3/METTL14 methyltransferase complex, is the most prevalent mRNA modification. m6A methylation regulates gene expression by influencing numerous aspects of mRNA metabolism, including pre‐mRNA processing, nuclear export, decay, and translation. The importance of m6A methylation as a mode of post‐transcriptional gene expression regulation is evident in the crucial roles m6A‐mediated gene regulation plays in numerous physiological and pathophysiological processes. Here, we review current knowledge on the mechanisms by which m6A exerts its functions and discuss recent advances that underscore the multifaceted role of m6A in the regulation of gene expression. We highlight advances in our understanding of the regulation of m6A deposition on mRNA and its context‐dependent effects on mRNA decay and translation, the role of m6A 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 m6A regulators in disease. 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.
RNA carries a diverse array of chemical modifications that play important roles in the regulation of gene expression. N6‐methyladenosine (m6A), installed onto mRNA by the METTL3/METTL14 methyltransferase complex, is the most prevalent mRNA modification. m6A methylation regulates gene expression by influencing numerous aspects of mRNA metabolism, including pre‐mRNA processing, nuclear export, decay, and translation. The importance of m6A methylation as a mode of post‐transcriptional gene expression regulation is evident in the crucial roles m6A‐mediated gene regulation plays in numerous physiological and pathophysiological processes. Here, we review current knowledge on the mechanisms by which m6A exerts its functions and discuss recent advances that underscore the multifaceted role of m6A in the regulation of gene expression. We highlight advances in our understanding of the regulation of m6A deposition on mRNA and its context‐dependent effects on mRNA decay and translation, the role of m6A 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 m6A regulators in disease. 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.
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.
Author He, Chuan
He, P Cody
AuthorAffiliation 1 Department of Chemistry Department of Biochemistry and Molecular Biology Institute for Biophysical Dynamics The University of Chicago Chicago IL USA
3 Howard Hughes Medical Institute The University of Chicago Chicago IL USA
2 Committee on Immunology The University of Chicago Chicago IL USA
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mRNA
m
A methylation
gene expression
RNA modifications
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SecondaryResourceType review_article
Snippet 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...
RNA carries a diverse array of chemical modifications that play important roles in the regulation of gene expression. N6‐methyladenosine (m6A), installed onto...
RNA carries a diverse array of chemical modifications that play important roles in the regulation of gene expression. N 6‐methyladenosine (m6A), installed onto...
SourceID pubmedcentral
proquest
wiley
springer
SourceType Open Access Repository
Aggregation Database
Publisher
SubjectTerms 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
Title m6A RNA methylation: from mechanisms to therapeutic potential
URI https://link.springer.com/article/10.15252/embj.2020105977
https://onlinelibrary.wiley.com/doi/abs/10.15252%2Fembj.2020105977
https://www.proquest.com/docview/2484193792
https://pubmed.ncbi.nlm.nih.gov/PMC7849164
Volume 40
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