YTHDF2 destabilizes m6A-containing RNA through direct recruitment of the CCR4–NOT deadenylase complex
説明
<jats:title>Abstract</jats:title><jats:p>Methylation at the <jats:italic>N</jats:italic>6 position of adenosine (m<jats:sup>6</jats:sup>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<jats:sup>6</jats:sup>A, the binding of which results in the alteration of the translation efficiency and stability of m<jats:sup>6</jats:sup>A-containing RNAs. However, the mechanism by which YTHDF proteins cause the degradation of m<jats:sup>6</jats:sup>A-containing RNAs is poorly understood. Here we report that m<jats:sup>6</jats:sup>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<jats:sup>6</jats:sup>A-containing RNAs by CAF1 and CCR4. Therefore, we have uncovered the mechanism of YTHDF2-mediated degradation of m<jats:sup>6</jats:sup>A-containing RNAs in mammalian cells.</jats:p>
収録刊行物
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- Nature Communications
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Nature Communications 7 (1), 12626-, 2016-08-25
Springer Science and Business Media LLC
