title: The dynamic N(1)-methyladenosine methylome in eukaryotic messenger RNA.
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.
authors: Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.|Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
authors: Dan
authors: D
authors: Dominissini
authors: Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.|Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
authors: Sigrid
authors: S
authors: Nachtergaele
authors: Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel.
authors: Sharon
authors: S
authors: Moshitch-Moshkovitz
authors: Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel.|Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors: Eyal
authors: E
authors: Peer
authors: Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel.
authors: Nitzan
authors: N
authors: Kol
authors: Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel.|Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors: Moshe Shay
authors: MS
authors: Ben-Haim
authors: Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.|Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
authors: Qing
authors: Q
authors: Dai
authors: Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel.
authors: Ayelet
authors: A
authors: Di Segni
authors: Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel.
authors: Mali
authors: M
authors: Salmon-Divon
authors: Department of Biochemistry and Molecular Biology, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
authors: Wesley C
authors: WC
authors: Clark
authors: Department of Biochemistry and Molecular Biology, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
authors: Guanqun
authors: G
authors: Zheng
authors: Department of Biochemistry and Molecular Biology, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
authors: Tao
authors: T
authors: Pan
authors: Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel.|The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel.
authors: Oz
authors: O
authors: Solomon
authors: Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel.
authors: Eran
authors: E
authors: Eyal
authors: Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel.
authors: Vera
authors: V
authors: Hershkovitz
authors: Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.|Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
authors: Dali
authors: D
authors: Han
authors: Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.|Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
authors: Louis C
authors: LC
authors: Doré
authors: Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel.|The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel.
authors: Ninette
authors: N
authors: Amariglio
authors: Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel.|Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors: Gideon
authors: G
authors: Rechavi
authors: Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.|Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.|Department of Biochemistry and Molecular Biology, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
authors: Chuan
authors: C
authors: He
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D045744:Cell Line, Tumor; D018387:Codon, Initiator / Q000235:genetics; D017124:Conserved Sequence; D044127:Epigenesis, Genetic; D019143:Evolution, Molecular; D020862:GC Rich Sequence / Q000235:genetics; D006801:Humans; D008745:Methylation; D051379:Mice; D009928:Organ Specificity; D010442:Peptide Chain Initiation, Translational / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae; D059467:Transcriptome / Q000235:genetics
chemical_list: D020121:5' Untranslated Regions; D018387:Codon, Initiator; D022821:RNA Splice Sites; D012333:RNA, Messenger; C002230:1-methyladenosine; D000241:Adenosine