The dynamic N1-methyladenosine methylome in eukaryotic messenger RNA

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...

Full description

Saved in:
Bibliographic Details
Published in:Nature (London) 2016-02, Vol.530 (7591), p.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: Article
Language:English
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0028-0836
1476-4687
DOI:10.1038/nature16998