The dynamic epitranscriptome: N6-methyladenosine and gene expression control

Nat Rev Mol Cell Biol. 2014 May;15(5):313-26. doi: 10.1038/nrm3785. Epub 2014 Apr 9.

Abstract

N(6)-methyladenosine (m(6)A) is a modified base that has long been known to be present in non-coding RNAs, ribosomal RNA, polyadenylated RNA and at least one mammalian mRNA. However, our understanding of the prevalence of this modification has been fundamentally redefined by transcriptome-wide m(6)A mapping studies, which have shown that m(6)A is present in a large subset of the transcriptome in specific regions of mRNA. This suggests that mRNA may undergo post-transcriptional methylation to regulate its fate and function, which is analogous to methyl modifications in DNA. Thus, the pattern of methylation constitutes an mRNA 'epitranscriptome'. The identification of adenosine methyltransferases ('writers'), m(6)A demethylating enzymes ('erasers') and m(6)A-binding proteins ('readers') is helping to define cellular pathways for the post-transcriptional regulation of mRNAs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / genetics
  • Adenosine / metabolism
  • AlkB Homolog 5, RNA Demethylase
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • Animals
  • Dioxygenases / genetics
  • Dioxygenases / metabolism
  • Epigenesis, Genetic*
  • Gene Expression
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Methylation
  • Methyltransferases / genetics
  • Methyltransferases / metabolism
  • Proteins / genetics
  • Proteins / metabolism
  • RNA Stability
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Transcriptome*

Substances

  • Membrane Proteins
  • Proteins
  • RNA, Messenger
  • N6-methyladenosine (m6A)
  • Dioxygenases
  • ALKBH5 protein, human
  • AlkB Homolog 5, RNA Demethylase
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human
  • Methyltransferases
  • METTL3 protein, human
  • Adenosine