Open AccessYTHDF2 destabilizes m6A-containing RNA through direct recruitment of the CCR4–NOT deadenylase complex
Author(s) -
Hao Du,
Ya Zhao,
Jinqiu He,
Yao Zhang,
Hairui Xi,
Mofang Liu,
Jinbiao Ma,
Ligang Wu
Publication year - 2016
Publication title -
nature communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.559
H-Index - 365
ISSN - 2041-1723
DOI - 10.1038/ncomms12626
Subject(s) - rna , microbiology and biotechnology , rna binding protein , long non coding rna , small nucleolar rna , biology , translation (biology) , protein subunit , guide rna , genetics , crispr , messenger rna , gene , cas9
Methylation at the N 6 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.