UPF1 promotes rapid degradation of m6A-containing RNAs. Boo et al.

Published: 9 May 2022| Version 1 | DOI: 10.17632/hmdttb83rd.1
Contributors:
Sung Ho Boo,
Yoon Ki Kim

Description

N6-methyladenosine (m6A) is the most prevalent internal modification in eukaryotic mRNAs and affects diverse RNA processing and metabolism. When YTHDF2, an m6A-recognizing protein, binds to m6A, it facilitates the destabilization of m6A-containing RNAs (m6A RNAs). Here, we demonstrate that upstream frameshift 1 (UPF1), a key factor for nonsense-mediated mRNA decay, interacts with YTHDF2, thereby triggering rapid degradation of m6A RNAs. The UPF1-mediated m6A RNA degradation depends on a specific interaction between UPF1 and N-terminal residues 101–168 of YTHDF2, UPF1 ATPase/helicase activities, and UPF1 interaction with proline-rich nuclear receptor coactivator 2 (PNRC2), a decapping-promoting factor preferentially involved in nonsense-mediated mRNA decay. Furthermore, transcriptome-wide analyses show that YTHDF2-bound mRNAs that are not substrates for HRSP12-RNase P/MRP–mediated endoribonucleolytic cleavage are destabilized with a higher dependency on UPF1. Collectively, our data indicate dynamic and multilayered regulation of the stability of m6A RNAs and highlight the multifaceted role of UPF1 in mRNA decay.

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Institutions

Korea University

Categories

Western Blot, Gel, Next Generation Sequencing

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