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

Author(s)
Schwartz, Schraga; Mumbach, Maxwell R.; Jovanovic, Marko; Mertins, Philipp; Shishkin, Alexander; Tabach, Yuval; Mikkelsen, Tarjei S.; Satija, Rahul; Ruvkun, Gary; Carr, Steven A.; Regev, Aviv; Agarwala, Sudeep; Lander, Eric Steven; Fink, Gerald R.; ... Show more Show less
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Abstract
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.
Date issued
2013-11
URI
http://hdl.handle.net/1721.1/106804
Department
Massachusetts Institute of Technology. Department of Biology; Whitehead Institute for Biomedical Research
Journal
Cell
Publisher
Elsevier B.V.
Citation
Schwartz, Schraga, Sudeep D. Agarwala, Maxwell R. Mumbach, Marko Jovanovic, Philipp Mertins, Alexander Shishkin, Yuval Tabach, et al. “High-Resolution Mapping Reveals a Conserved, Widespread, Dynamic mRNA Methylation Program in Yeast Meiosis.” Cell 155, no. 6 (December 2013): 1409-1421.
Version: Author's final manuscript
ISSN
00928674

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