YTHDF2 promotes mitotic entry and is regulated by cell cycle mediators

文献类型： 外文期刊

第一作者： Fei, Qili

作者： Fei, Qili;Zou, Zhongyu;Roundtree, Ian A.;Sun, Hui-Lung;He, Chuan;Fei, Qili;Zou, Zhongyu;Roundtree, Ian A.;Sun, Hui-Lung;He, Chuan;Fei, Qili;Roundtree, Ian A.;Roundtree, Ian A.;He, Chuan;Roundtree, Ian A.;He, Chuan

作者机构：

期刊名称：PLOS BIOLOGY （ 影响因子：8.029； 五年影响因子：9.57 ）

ISSN： 1544-9173

年卷期： 2020 年 18 卷 4 期

页码：

收录情况： SCI

摘要： The N-6-methyladenosine (m(6)A) modification regulates mRNA stability and translation. Here, we show that transcriptomic m(6)A modification can be dynamic and the m(6)A reader protein YTH N-6-methyladenosine RNA binding protein 2 (YTHDF2) promotes mRNA decay during cell cycle. Depletion of YTHDF2 in HeLa cells leads to the delay of mitotic entry due to overaccumulation of negative regulators of cell cycle such as Wee1-like protein kinase (WEE1). We demonstrate that WEE1 transcripts contain m(6)A modification, which promotes their decay through YTHDF2. Moreover, we found that YTHDF2 protein stability is dependent on cyclin-dependent kinase 1 (CDK1) activity. Thus, CDK1, YTHDF2, and WEE1 form a feedforward regulatory loop to promote mitotic entry. We further identified Cullin 1 (CUL1), Cullin 4A (CUL4A), damaged DNA-binding protein 1 (DDB1), and S-phase kinase-associated protein 2 (SKP2) as components of E3 ubiquitin ligase complexes that mediate YTHDF2 proteolysis. Our study provides insights into how cell cycle mediators modulate transcriptomic m(6)A modification, which in turn regulates the cell cycle.

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