2. Academic Validation
  3. YTHDF2 destabilizes m(6)A-containing RNA through direct recruitment of the CCR4-NOT deadenylase complex

YTHDF2 destabilizes m(6)A-containing RNA through direct recruitment of the CCR4-NOT deadenylase complex

  • Nat Commun. 2016 Aug 25;7:12626. doi: 10.1038/ncomms12626.
Hao Du 1 2 3,  Ya Zhao 1 2 3,  Jinqiu He 4,  Yao Zhang 5,  Hairui Xi 1 2 3 6,  Mofang Liu 3,  Jinbiao Ma 4,  Ligang Wu 1 2 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Molecular Biology, National Center for Protein Science Shanghai, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
  • 2 CAS-Shanghai Science Research Center, Chinese Academy of Sciences, Shanghai 201204, China.
  • 3 Shanghai Key Laboratory of Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
  • 4 State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Department of Biochemistry, Institute of Plant Biology, School of Life Sciences, Fudan University, Shanghai 200433, China.
  • 5 Shanghai Institute of Planned Parenthood Research, Shanghai 200032, China.
  • 6 School of Life Sciences, Shanghai University, 333 Nanchen Road, Shanghai 200444, China.
PMID: 27558897 DOI: 10.1038/ncomms12626
Abstract

Methylation at the N6 position of adenosine (m(6)A) is the most abundant RNA modification within protein-coding and long noncoding RNAs in eukaryotes and is a reversible process with important biological functions. YT521-B homology domain family (YTHDF) proteins are the readers of m(6)A, the binding of which results in the alteration of the translation efficiency and stability of m(6)A-containing RNAs. However, the mechanism by which YTHDF proteins cause the degradation of m(6)A-containing RNAs is poorly understood. Here we report that m(6)A-containing RNAs exhibit accelerated deadenylation that is mediated by the CCR4-NOT deadenylase complex. We further show that YTHDF2 recruits the CCR4-NOT complex through a direct interaction between the YTHDF2 N-terminal region and the SH domain of the CNOT1 subunit, and that this recruitment is essential for the deadenylation of m(6)A-containing RNAs by CAF1 and CCR4. Therefore, we have uncovered the mechanism of YTHDF2-mediated degradation of m(6)A-containing RNAs in mammalian cells.

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