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.
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YTHDF2 通过直接招募 CCR4-NOT 去腺苷酶复合物来破坏含有 m(6)A 的 RNA 的稳定性。
DOI：
10.1038/ncomms12626
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发表时间：
2016-08-25
影响因子：
16.6
通讯作者：
Wu, Ligang
中科院分区：
文献类型：
--
作者：
Du, Hao;Zhao, Ya;He, Jinqiu;Zhang, Yao;Xi, Hairui;Liu, Mofang;Ma, Jinbiao;Wu, Ligang
腺苷N6位甲基化（m6A）是真核生物蛋白编码RNA和长链非编码RNA中最丰富的RNA修饰，是一个具有重要生物学功能的可逆过程。YT521-B同源结构域家族（YTHDF）蛋白是m6A的读者，与m6A的结合会改变含m6A rna的翻译效率和稳定性。然而，YTHDF蛋白导致含m6a rna降解的机制尚不清楚。在这里，我们报道含有m6a的rna表现出由CCR4-NOT死烯化酶复合物介导的加速死烯化。我们进一步表明，YTHDF2通过YTHDF2 n端区域和CNOT1亚基SH结构域之间的直接相互作用招募CCR4 - not复合物，并且这种招募对于CAF1和CCR4对含有m6a的rna的死化至关重要。因此，我们已经揭示了哺乳动物细胞中ythdf2介导的含m6a rna降解的机制。YTHDF家族蛋白能够结合并调节甲基化N6 RNA的稳定性。本文作者表明，m6A RNA稳定性的下降是通过YTHDF蛋白直接募集CCR4-NOT deadenylase复合物介导的。
Methylation at the N6 position of adenosine (m6A) 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 m6A, the binding of which results in the alteration of the translation efficiency and stability of m6A-containing RNAs. However, the mechanism by which YTHDF proteins cause the degradation of m6A-containing RNAs is poorly understood. Here we report that m6A-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 m6A-containing RNAs by CAF1 and CCR4. Therefore, we have uncovered the mechanism of YTHDF2-mediated degradation of m6A-containing RNAs in mammalian cells. The YTHDF family of proteins are able to bind and regulate the stability of methylated N6 RNA. Here the authors show that this decreased m6A RNA stability is mediated by direct recruitment of the CCR4–NOT deadenylase complex through YTHDF proteins.
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影响因子：
4.1
作者：
Kang, Hyun-Jun;Jeong, Sook-Jin;Yun, Cheol-Won
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Yun, Cheol-Won
影响因子：
56.9
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Chang, Howard Y.
影响因子：
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作者：
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