N6-methyladenosine modification in mRNA: machinery, function and implications for health and diseases

FEBS J. 2016 May;283(9):1607-30. doi: 10.1111/febs.13614. Epub 2015 Dec 31.


N6-methyladenosine (m(6) A) modification in mRNA is extremely widespread, and functionally modulates the eukaryotic transcriptome to influence mRNA splicing, export, localization, translation, and stability. Methylated adenines are present in a large subset of mRNAs and long noncoding RNAs (lncRNAs). Methylation is reversible, and this is accomplished by the orchestrated action of highly conserved methyltransferase (m(6) A writer) and demethylase (m(6) A eraser) enzymes to shape the cellular 'epitranscriptome'. The engraved 'methyl code' is subsequently decoded and executed by a group of m(6) A reader/effector components, which, in turn, govern the fate of the modified transcripts, thereby dictating their potential for translation. Reversible mRNA methylation thus adds another layer of regulation at the post-transcriptional level in the gene expression programme of eukaryotes that finely sculpts a highly dynamic proteome in order to respond to diverse cues during cellular differentiation, immune tolerance, and neuronal signalling.

Keywords: epitranscriptomics; m6A effector; m6A methylation; m6A reader; m6A writer; mRNA modification.

Publication types

  • Review

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / metabolism
  • Cell Differentiation
  • Eukaryotic Cells / cytology
  • Eukaryotic Cells / metabolism
  • Humans
  • Methylation
  • Methyltransferases / genetics
  • Methyltransferases / metabolism*
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / pathology
  • Oxidoreductases, N-Demethylating / genetics
  • Oxidoreductases, N-Demethylating / metabolism*
  • RNA Splicing
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Signal Transduction
  • Transcription, Genetic


  • RNA, Long Noncoding
  • RNA, Messenger
  • N-methyladenosine
  • Oxidoreductases, N-Demethylating
  • 6-methyladenine mRNA methyltransferase
  • Methyltransferases
  • Adenosine