Epitranscriptomic modifications on mRNA play an important role in RNA function and can impact gene expression. Our current understanding of epitranscriptomic gene regulation is largely based upon studies of N6-methyladenosine (m6A), however a number of other mRNA modification have been identified. Here, we apply a chemical proteomics approach to investigate readers of N1-methyladenosine (m1A), a poorly characterized modification on mammalian mRNA. We find that YTHDF proteins, known m6A readers, also recognize m1A-modified sequences in a methylation-specific manner. Biochemical characterization of m1A-modified RNA and YTHDF1/2 demonstrates that these interactions exhibit comparable affinity to m6A-binding events, and occur in diverse sequence contexts. Further, we deplete YTHDF2 in cells to show that the stability of m1A-modified transcripts is regulated by this protein. Our results shed light on the function of m1A on mRNA, and provide a mechanistic framework to further evaluate the role of m1A in biological processes.

YTHDF2 reads N1-methyladenosine (m1A)-modified RNA to destabilize substrate transcripts

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.