除了DNA转录水平的调控，胚胎干细胞全能性的转录后调控近年来引起广泛关注。我们在2014年报道发现pre-mRNA3'末端加工复合体中的一个蛋白Fip1通过调控众多mRNA在不同3'末端位点加polyA尾巴（alternative polyadenylation，APA)而参与胚胎干细胞全能性维持，首次强调mRNA3'末端加工和APA调控这一重要的基因转录后调控机制在干细胞中的功能。在此基础上，本项目将系统研究pre-mRNA3'末端加工复合体中的其它核心蛋白在胚胎干细胞全能性维持中的功能以及机制，进一步探索挖掘mRNA3'末端加工和APA这一转录后调控机制在高级复杂生物体的发育分化中所扮演的重要作用。

How the Embroynic Stem Cells (ESC) maintain the ability of self-renewal is a long-standing question, current understanding is largely restricted to gene regulation at transcription level, while recent studies have shown that post-transcriptional gene regulation may play more important role than previously appreciated. In 2014, we reported Fip1, a component of pre-mRNA 3' processing complex, promotes ESC self-renewal by regulating a large number of mRNA APA (alternative polyadenylation), the results demonstrate the importance of post-transcriptional gene regulation especially APA regulation in stem cell function. As follow-up studies, this project will systematically analyze the mechanism and functional significance of other essential pre-mRNA 3' processing factors in regulating ESC self-renewal. Successful completion of the proposed study will provide novel and significant insight into the emerging post-transcriptional gene regulation especially mRNA 3'end processing and APA regulation in stem cell and animal development.