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, Chuan He

Research output: Contribution to journalArticlepeer-review


Gene expression can be regulated post-transcriptionally through dynamic and reversible RNA modifications. A recent noteworthy example is N6 -methyladenosine (m6 A), which affects messenger RNA (mRNA) localization, stability, translation and splicing. Here we report on a new mRNA modification, N1-methyladenosine (m1 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 m1 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 m1 A in promoting translation of methylated mRNA.

Original languageEnglish
Pages (from-to)441-446
Number of pages6
Issue number7591
StatePublished - 25 Feb 2016


FundersFunder number
Searle Funds at The Chicago Community Trust
National Institutes of HealthHG008688, GM71440
National Institute of General Medical SciencesR01GM113194
Damon Runyon Cancer Research FoundationDRG-2215-15, HG006699
Human Frontier Science Program
Flight Attendant Medical Research Institute
Iowa Science Foundation1667/12
Israel Science Foundation
Israeli Centers for Research Excellence41/11, 1796/12


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