title: High-resolution mapping reveals a conserved, widespread, dynamic mRNA methylation program in yeast meiosis.
abstract: 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.
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: Schraga
authors.initials: S
authors.lastname: Schwartz
authors.forename: Sudeep D
authors.initials: SD
authors.lastname: Agarwala
authors.forename: Maxwell R
authors.initials: MR
authors.lastname: Mumbach
authors.forename: Marko
authors.initials: M
authors.lastname: Jovanovic
authors.forename: Philipp
authors.initials: P
authors.lastname: Mertins
authors.forename: Alexander
authors.initials: A
authors.lastname: Shishkin
authors.forename: Yuval
authors.initials: Y
authors.lastname: Tabach
authors.forename: Tarjei S
authors.initials: TS
authors.lastname: Mikkelsen
authors.forename: Rahul
authors.initials: R
authors.lastname: Satija
authors.forename: Gary
authors.initials: G
authors.lastname: Ruvkun
authors.forename: Steven A
authors.initials: SA
authors.lastname: Carr
authors.forename: Eric S
authors.initials: ES
authors.lastname: Lander
authors.forename: Gerald R
authors.initials: GR
authors.lastname: Fink
authors.forename: Aviv
authors.initials: A
authors.lastname: Regev
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D002466:Cell Nucleolus / Q000378:metabolism; D016681:Genome, Fungal; D008540:Meiosis; D008745:Methylation; D009687:Nuclear Proteins / Q000378:metabolism; D012331:RNA, Fungal / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D012440:Saccharomyces / Q000166:cytology* / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D012359:tRNA Methyltransferases / Q000378:metabolism
chemical_list: C080326:IME1 protein, S cerevisiae; D009687:Nuclear Proteins; D012331:RNA, Fungal; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C010223:N-methyladenosine; D012359:tRNA Methyltransferases; D000241:Adenosine