Cell
Volume 155, Issue 6, 5 December 2013, Pages 1409-1421
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High-Resolution Mapping Reveals a Conserved, Widespread, Dynamic mRNA Methylation Program in Yeast Meiosis

https://doi.org/10.1016/j.cell.2013.10.047Get rights and content
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Highlights

  • 1,308 high-confidence RNA methylation sites at nearly single-nucleotide resolution

  • Temporal methylation profiles vary during meiosis depending on cis and trans factors

  • Nucleolar colocalization of methylation components is essential for methylation

  • M6A “readers,” “writers,” and characteristics are highly conserved from yeast to mammals

Summary

N6-methyladenosine (m6A) 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 m6A 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.

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These authors contributed equally to this work