RNF219 interacts with CCR4-NOT in regulating stem cell differentiation.

RNF219 interacts with CCR4-NOT in regulating stem cell differentiation.
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RNF219 与 CCR4 相互作用,调节干细胞分化。

DOI:
10.1093/jmcb/mjaa061
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发表时间:
2020-10-26
影响因子:
5.5
通讯作者:
Luo Z
Luo Z
中科院分区:
生物学1区
文献类型:
--
作者:
Du H;Chen C;Wang Y;Yang Y;Che Z;Liu X;Meng S;Guo C;Xu M;Fang H;Wang F;Lin C;Luo Z

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RNA稳定性的调节在基因表达控制中起着至关重要的作用。脱腺苷酸化是大多数RNA衰变事件的初始限速步骤。在这里,我们表明,环指蛋白219(RNF 219)与CCR 4-NOT deadenylase复合物相互作用。RNF 219-CCR 4-NOT在体外表现出去腺苷化活性。RNA-seq分析鉴定了一些2细胞特异性基因和神经元基因在RNF 219敲低后显著下调,而在小鼠胚胎干(ES)细胞中CCR 4-NOT亚基hocT 10耗尽后上调。RNF 219耗竭导致ES细胞分化过程中神经元谱系定型受损。我们的研究表明,RNF 219是一个新的相互作用的伴侣CCR 4-NOT和所需的维持ES细胞的多能性。
Regulation of RNA stability plays a crucial role in gene expression control. Deadenylation is the initial rate-limiting step for the majority of RNA decay events. Here, we show that RING finger protein 219 (RNF219) interacts with the CCR4–NOT deadenylase complex. RNF219–CCR4–NOT exhibits deadenylation activity in vitro. RNA-seq analyses identify some of the 2-cell-specific genes and the neuronal genes significantly downregulated upon RNF219 knockdown, while upregulated after depletion of the CCR4–NOT subunit CNOT10 in mouse embryonic stem (ES) cells. RNF219 depletion leads to impaired neuronal lineage commitment during ES cell differentiation. Our study suggests that RNF219 is a novel interacting partner of CCR4–NOT and required for maintenance of ES cell pluripotency.
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。
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