The dynamic N1-methyladenosine methylome in eukaryotic messenger RNA

Dan Dominissini (), Sigrid Nachtergaele, Sharon Moshitch-Moshkovitz, Eyal Peer, Nitzan Kol, Moshe Shay Ben-Haim, Qing Dai, Ayelet Di Segni, Mali Salmon-Divon, Wesley C. Clark, Guanqun Zheng, Tao Pan, Oz Solomon, Eran Eyal, Vera Hershkovitz, Dali Han, Louis C. Doré, Ninette Amariglio, Gideon Rechavi () and Chuan He ()
Additional contact information
Dan Dominissini: The University of Chicago
Sigrid Nachtergaele: The University of Chicago
Sharon Moshitch-Moshkovitz: Cancer Research Center, Chaim Sheba Medical Center
Eyal Peer: Cancer Research Center, Chaim Sheba Medical Center
Nitzan Kol: Cancer Research Center, Chaim Sheba Medical Center
Moshe Shay Ben-Haim: Cancer Research Center, Chaim Sheba Medical Center
Qing Dai: The University of Chicago
Ayelet Di Segni: Cancer Research Center, Chaim Sheba Medical Center
Mali Salmon-Divon: Cancer Research Center, Chaim Sheba Medical Center
Wesley C. Clark: The University of Chicago
Guanqun Zheng: The University of Chicago
Tao Pan: The University of Chicago
Oz Solomon: Cancer Research Center, Chaim Sheba Medical Center
Eran Eyal: Cancer Research Center, Chaim Sheba Medical Center
Vera Hershkovitz: Cancer Research Center, Chaim Sheba Medical Center
Dali Han: The University of Chicago
Louis C. Doré: The University of Chicago
Ninette Amariglio: Cancer Research Center, Chaim Sheba Medical Center
Gideon Rechavi: Cancer Research Center, Chaim Sheba Medical Center
Chuan He: The University of Chicago

Nature, 2016, vol. 530, issue 7591, 441-446

Abstract: Abstract Gene expression can be regulated post-transcriptionally through dynamic and reversible RNA modifications. A recent noteworthy example is N6-methyladenosine (m6A), which affects messenger RNA (mRNA) localization, stability, translation and splicing. Here we report on a new mRNA modification, N1-methyladenosine (m1A), 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 m1A 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 m1A in promoting translation of methylated mRNA.

Date: 2016
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DOI: 10.1038/nature16998

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