The dynamic N(1)-methyladenosine methylome in eukaryotic messenger RNA

Nature. 2016 Feb 25;530(7591):441-6. doi: 10.1038/nature16998. Epub 2016 Feb 10.


Gene expression can be regulated post-transcriptionally through dynamic and reversible RNA modifications. A recent noteworthy example is N(6)-methyladenosine (m(6)A), which affects messenger RNA (mRNA) localization, stability, translation and splicing. Here we report on a new mRNA modification, N(1)-methyladenosine (m(1)A), that occurs on thousands of different gene transcripts in eukaryotic cells, from yeast to mammals, at an estimated average transcript stoichiometry of 20% in humans. Employing newly developed sequencing approaches, we show that m(1)A is enriched around the start codon upstream of the first splice site: it preferentially decorates more structured regions around canonical and alternative translation initiation sites, is dynamic in response to physiological conditions, and correlates positively with protein production. These unique features are highly conserved in mouse and human cells, strongly indicating a functional role for m(1)A in promoting translation of methylated mRNA.

Publication types

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

MeSH terms

  • 5' Untranslated Regions / genetics
  • Adenosine / analogs & derivatives*
  • Adenosine / metabolism
  • Animals
  • Base Sequence
  • Cell Line
  • Cell Line, Tumor
  • Codon, Initiator / genetics
  • Conserved Sequence
  • Epigenesis, Genetic
  • Evolution, Molecular
  • GC Rich Sequence / genetics
  • Humans
  • Methylation
  • Mice
  • Organ Specificity
  • Peptide Chain Initiation, Translational / genetics
  • RNA Splice Sites / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Saccharomyces cerevisiae
  • Transcriptome / genetics


  • 5' Untranslated Regions
  • Codon, Initiator
  • RNA Splice Sites
  • RNA, Messenger
  • 1-methyladenosine
  • Adenosine

Associated data

  • GEO/GSE70485