YTHDF2 destabilizes m6A-containing RNA through direct recruitment of the CCR4-NOT deadenylase complex

被引：1437

作者：

Du, Hao ^{[1
,2
,3
]}

Zhao, Ya ^{[1
,2
,3
]}

He, Jinqiu ^{[4
]}

Zhang, Yao ^{[5
]}

Xi, Hairui ^{[1
,2
,3
,6
]}

Liu, Mofang ^{[3
]}

Ma, Jinbiao ^{[4
]}

Wu, Ligang ^{[1
,2
,3
]}

机构：

[1] Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci,Inst Biochem & Cell Biol, State Key Lab Mol Biol,Natl Ctr Prot Sci Shanghai, 320 Yue Yang Rd, Shanghai 200031, Peoples R China

[2] Chinese Acad Sci, CAS Shanghai Sci Res Ctr, Shanghai 201204, Peoples R China

[3] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai Key Lab Mol Androl,State Key Lab Mol Bio, Shanghai 200031, Peoples R China

[4] Fudan Univ, Sch Life Sci, Inst Plant Biol,Dept Biochem, State Key Lab Genet Engn,Collaborat Innovat Ctr G, Shanghai 200433, Peoples R China

[5] Shanghai Inst Planned Parenthood Res, Shanghai 200032, Peoples R China

[6] Shanghai Univ, Sch Life Sci, 333 Nanchen Rd, Shanghai 200444, Peoples R China

来源：

NATURE COMMUNICATIONS | 2016年 / 7卷

基金：

中国博士后科学基金; 中国国家自然科学基金;

关键词：

MESSENGER-RNA; NUCLEAR-RNA; N-6-METHYLADENOSINE; BINDING; PROTEIN; DOMAIN; REVEALS; GENE; RESOLUTION; DECAY;

D O I：

10.1038/ncomms12626

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页数：11

共 57 条

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