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Cell DOI:10.1016/j.cell.2013.10.047

High-resolution mapping reveals a conserved, widespread, dynamic mRNA methylation program in yeast meiosis.

Publication TypeJournal Article
Year of Publication2013
AuthorsSchwartz, S, Agarwala, SD, Mumbach, MR, Jovanovic, M, Mertins, P, Shishkin, A, Tabach, Y, Mikkelsen, TS, Satija, R, Ruvkun, G, Carr, SA, Lander, ES, Fink, GR, Regev, A
Date Published2013 Dec 05
KeywordsAdenosine, Cell Nucleolus, Genome, Fungal, Meiosis, Methylation, Nuclear Proteins, RNA, Fungal, RNA, Messenger, Saccharomyces, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Transcription Factors, tRNA Methyltransferases

N(6)-methyladenosine (m(6)A) is the most ubiquitous mRNA base modification, but little is known about its precise location, temporal dynamics, and regulation. Here, we generated genomic maps of m(6)A sites in meiotic yeast transcripts at nearly single-nucleotide resolution, identifying 1,308 putatively methylated sites within 1,183 transcripts. We validated eight out of eight methylation sites in different genes with direct genetic analysis, demonstrated that methylated sites are significantly conserved in a related species, and built a model that predicts methylated sites directly from sequence. Sites vary in their methylation profiles along a dense meiotic time course and are regulated both locally, via predictable methylatability of each site, and globally, through the core meiotic circuitry. The methyltransferase complex components localize to the yeast nucleolus, and this localization is essential for mRNA methylation. Our data illuminate a conserved, dynamically regulated methylation program in yeast meiosis and provide an important resource for studying the function of this epitranscriptomic modification.


Alternate JournalCell
PubMed ID24269006
PubMed Central IDPMC3956118
Grant ListR01 CA119176 / CA / NCI NIH HHS / United States
DP1 CA174427 / CA / NCI NIH HHS / United States
T32 NS007292 / NS / NINDS NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
P50 HG006193 / HG / NHGRI NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
R01 GM035010 / GM / NIGMS NIH HHS / United States
GM035010 / GM / NIGMS NIH HHS / United States
R01 GM098647 / GM / NIGMS NIH HHS / United States