CFIm25 regulates human stem cell function independently of its role in mRNA alternative polyadenylation.
CFIm25 regulates human stem cell function independently of its role in mRNA alternative polyadenylation.
复制标题
DOI：
10.1080/15476286.2022.2071025
复制
发表时间：
2022
期刊：
影响因子：
4.1
通讯作者：
Yao, Chengguo
中科院分区：
文献类型：
--
作者：
Ran, Yi;Huang, Shanshan;Shi, Junjie;Feng, Qiumin;Deng, Yanhui;Xiang, Andy Peng;Yao, Chengguo
CFIm 25是一种典型的mRNA 3'加工因子，它通过调节mRNA的交替多聚腺苷酸化（阿帕）而发挥多种生理功能。在这里，我们使用CRISPR/Cas9介导的基因编辑方法在人胚胎干细胞（hESC）中进行CFIm 25，并获得了三种基因敲低/突变细胞系。CFIm 25基因编辑导致hESC的增殖率更高，分化潜力受损，这些影响可能直接受靶基因（包括多能性因子rex 1）的调节。从机制上讲，我们意外地发现CFIm 25基因表达的扰动并不显著影响细胞mRNA 3'加工效率和阿帕谱。相反，我们提供的证据表明，CFIm 25可能会影响RNA聚合酶II（RNAPII）在转录基因体的占有率，并促进一组与细胞增殖和/或分化相关的转录本的表达水平。综上所述，这些结果揭示了CFIm 25 β s调节决定细胞命运的新机制，并提供了哺乳动物基因转录过程可能受mRNA 3'加工因子调控的证据。
It has recently been shown that CFIm25, a canonical mRNA 3’ processing factor, could play a variety of physiological roles through its molecular function in the regulation of mRNA alternative polyadenylation (APA). Here, we used CRISPR/Cas9-mediated gene editing approach in human embryonic stem cells (hESCs) for CFIm25, and obtained three gene knockdown/mutant cell lines. CFIm25 gene editing resulted in higher proliferation rate and impaired differentiation potential for hESCs, with these effects likely to be directly regulated by the target genes, including the pluripotency factor rex1. Mechanistically, we unexpected found that perturbation in CFIm25 gene expression did not significantly affect cellular mRNA 3’ processing efficiency and APA profile. Rather, we provided evidences that CFIm25 may impact RNA polymerase II (RNAPII) occupancy at the body of transcribed genes, and promote the expression level of a group of transcripts associated with cellular proliferation and/or differentiation. Taken together, these results reveal novel mechanisms underlying CFIm25ʹs modulation in determination of cell fate, and provide evidence that the process of mammalian gene transcription may be regulated by an mRNA 3’ processing factor.
登录
查看更多内容
影响因子：
64.8
作者：
通讯作者：
--
3'RNA聚合酶II CTD上Ser2的前MRNA的末端形成和在人类细胞中相互耦合。
影响因子：
10.5
作者：
Davidson L;Muniz L;West S
通讯作者：
West S
影响因子：
16
作者：
Caizzi, Livia;Monteiro-Martins, Sara;Cramer, Patrick
通讯作者：
Cramer, Patrick
影响因子：
14.9
作者：
Katahira J;Okuzaki D;Inoue H;Yoneda Y;Maehara K;Ohkawa Y
通讯作者：
Ohkawa Y
影响因子：
4.8
作者：
El Kaderi, Belal;Medler, Scott;Ansari, Athar
通讯作者：
Ansari, Athar