High-Resolution Mapping Reveals a Conserved, Widespread, Dynamic mRNA Methylation Program in Yeast Meiosis

• Main Authors: Schwartz, Schraga (Author), Mumbach, Maxwell R (Author), Jovanovic, Marko (Author), Mertins, Philipp (Author), Shishkin, Alexander (Author), Tabach, Yuval (Author), Mikkelsen, Tarjei S (Author), Satija, Rahul (Author), Ruvkun, Gary (Author), Carr, Steven A (Author), Regev, Aviv (Author), Agarwala, Sudeep (Contributor), Lander, Eric Steven (Contributor), Fink, Gerald R. (Contributor)
• Other Authors: Massachusetts Institute of Technology. Department of Biology (Contributor), Whitehead Institute for Biomedical Research (Contributor), Regiv, Aviv (Contributor)
• Format: Article
• Language: English
• Published: Elsevier B.V., 2017-01-31T16:07:37Z.
• Subjects: Article
• Online Access: Get fulltext

N[superscript 6]-methyladenosine (m[superscript 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[superscript 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.
American Cancer Society (Professor of Genetics)
National Institutes of Health (U.S.) (NIH Grant GM035010)
National Institutes of Health (U.S.) (NIH Grant U54 HG003067)
Broad Institute of MIT and Harvard (Funds)
National Human Genome Research Institute (U.S.) (NHGRI Pioneer Award)
Howard Hughes Medical Institute
Human Frontier Science Program (Strasbourg, France) (Fellowship)