The dynamic N1-methyladenosine methylome in eukaryotic messenger RNA

• Published in: Nature (London) Vol. 530; no. 7591; pp. 441 - 446
• Main Authors: Dominissini, Dan, Nachtergaele, Sigrid, Moshitch-Moshkovitz, Sharon, Peer, Eyal, Kol, Nitzan, Ben-Haim, Moshe Shay, Dai, Qing, Di Segni, Ayelet, Salmon-Divon, Mali, Clark, Wesley C., Zheng, Guanqun, Pan, Tao, Solomon, Oz, Eyal, Eran, Hershkovitz, Vera, Han, Dali, Doré, Louis C., Amariglio, Ninette, Rechavi, Gideon, He, Chuan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.02.2016
• Subjects: 631/337/1645/2570; 631/337/176; 631/92/500; Humanities and Social Sciences; multidisciplinary; Science
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature16998

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. Here the m 1 A modification is discovered in messenger RNA and mapped at the transcriptome-wide level; the modification is conserved, dynamic, accumulates in structured regions around translation initiation sites upstream of the first splice site, and correlates with higher protein expression. The m 1 A RNA modification The N 6 -methyladenosine (m 6 A) modification of RNA has been subject to intensive examination since it was recognized to be widespread throughout the transcriptome. In a new study by Chuan He and colleagues, the significance of a different messenger RNA modification, N 1 -methyladenosine (m 1 A), is probed on the transcriptome-wide level. Although the modification is dynamic, they find it accumulates in structured regions surrounding both canonical and alternative translation initiation sites, and its presence correlates with higher protein expression.