2. Academic Validation
  3. The dynamic N(1)-methyladenosine methylome in eukaryotic messenger RNA

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

  • Nature. 2016 Feb 25;530(7591):441-6. doi: 10.1038/nature16998.
Dan Dominissini 1 2,  Sigrid Nachtergaele 1 2,  Sharon Moshitch-Moshkovitz 3,  Eyal Peer 3 4,  Nitzan Kol 3,  Moshe Shay Ben-Haim 3 4,  Qing Dai 1 2,  Ayelet Di Segni 3,  Mali Salmon-Divon 3,  Wesley C Clark 5,  Guanqun Zheng 5,  Tao Pan 5,  Oz Solomon 3 6,  Eran Eyal 3,  Vera Hershkovitz 3,  Dali Han 1 2,  Louis C Doré 1 2,  Ninette Amariglio 3 6,  Gideon Rechavi 3 4,  Chuan He 1 2 5
Affiliations

Affiliations

  • 1 Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
  • 2 Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
  • 3 Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel.
  • 4 Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
  • 5 Department of Biochemistry and Molecular Biology, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
  • 6 The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel.
PMID: 26863196 DOI: 10.1038/nature16998
Abstract

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.

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