You are here

Cell Rep DOI:10.1016/j.celrep.2014.05.048

Perturbation of m6A writers reveals two distinct classes of mRNA methylation at internal and 5' sites.

Publication TypeJournal Article
Year of Publication2014
AuthorsSchwartz, S, Mumbach, MR, Jovanovic, M, Wang, T, Maciag, K, G Bushkin, G, Mertins, P, Ter-Ovanesyan, D, Habib, N, Cacchiarelli, D, Sanjana, NE, Freinkman, E, Pacold, ME, Satija, R, Mikkelsen, TS, Hacohen, N, Zhang, F, Carr, SA, Lander, ES, Regev, A
JournalCell Rep
Date Published2014 Jul 10
Keywords5' Untranslated Regions, Animals, HEK293 Cells, Humans, Methylation, Methyltransferases, Mice, RNA Processing, Post-Transcriptional, RNA Stability, RNA, Messenger

N6-methyladenosine (m6A) is a common modification of mRNA with potential roles in fine-tuning the RNA life cycle. Here, we identify a dense network of proteins interacting with METTL3, a component of the methyltransferase complex, and show that three of them (WTAP, METTL14, and KIAA1429) are required for methylation. Monitoring m6A levels upon WTAP depletion allowed the definition of accurate and near single-nucleotide resolution methylation maps and their classification into WTAP-dependent and -independent sites. WTAP-dependent sites are located at internal positions in transcripts, topologically static across a variety of systems we surveyed, and inversely correlated with mRNA stability, consistent with a role in establishing "basal" degradation rates. WTAP-independent sites form at the first transcribed base as part of the cap structure and are present at thousands of sites, forming a previously unappreciated layer of transcriptome complexity. Our data shed light on the proteomic and transcriptional underpinnings of this RNA modification.


Alternate JournalCell Rep
PubMed ID24981863
PubMed Central IDPMC4142486
Grant ListT32 GM007287 / GM / NIGMS NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
T32 GM007598 / GM / NIGMS NIH HHS / United States
P30 CA014051 / CA / NCI NIH HHS / United States
T32 GM007753 / GM / NIGMS NIH HHS / United States
DP1 CA174427 / CA / NCI NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
DP1 MH100706 / MH / NIMH NIH HHS / United States
P50 HG006193 / HG / NHGRI NIH HHS / United States