m1A and m6A modifications function cooperatively to facilitate rapid mRNA degradation

Sung Ho Boo, Hongseok Ha, Yoon Ki Kim

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

N6-Methyladenosine (m6A), the most abundant internal mRNA modification, affects multiple steps in gene expression. Mechanistically, the binding of YTHDF2 to m6A on mRNAs elicits rapid mRNA degradation by recruiting several RNA degrading enzymes. Here, we show that N1-methyladenosine (m1A), another type of RNA modification, accelerates rapid m6A RNA degradation. We identify HRSP12 as an RNA-binding protein that recognizes m1A. The binding of HRSP12 to m1A promotes efficient interaction of YTHDF2 with m6A, consequently facilitating endoribonucleolytic cleavage via the RNase P/MRP complex. Transcriptome-wide analyses also reveal that mRNAs harboring both m1A and m6A are downregulated in an HRSP12-dependent manner compared with mRNAs harboring m6A only. Accordingly, a subset of endogenous circular RNAs that harbor m6A and associate with YTHDF2 in an HRSP12-dependent manner is also subjected to m1A-facilitated rapid degradation. Together, our observations provide compelling evidence for crosstalk between different RNA modifications.

Original languageEnglish
Article number111317
JournalCell Reports
Volume40
Issue number10
DOIs
Publication statusPublished - 2022 Sept 6
Externally publishedYes

Bibliographical note

Funding Information:
We thank Dr. Ligang Wu for providing the m 6 A reporter plasmids. This work was supported by a National Research Foundation (NRF) of Korea grant funded by the Korean Government ( Ministry of Science, ICT, and Future Planning ; NRF-2015R1A3A2033665 , NRF-2018R1A5A1024261 , and NRF-2022M3E5F1017965 ).

Publisher Copyright:
© 2022 The Authors

Keywords

  • CP: Molecular biology
  • HRSP12
  • N-methyladenosine
  • N-methyladenosine
  • RNase P/MRP
  • YTHDF2
  • mA
  • mA
  • mRNA decay

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology

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