微RNA关键结合蛋白的功能与机制研究

摘要

Based on our proposed research plan, we have screened the functional proteins in piRNA and miRNA pathways and studied their roles and mechanisms. The main progresses include: (1) studied the regulation of MIWI/piRNA machinery and the biological significance underlying; (2) revealed pachytene piRNAs, in complex with MIWI and deadenylase CAF1, mediate massive mRNA degradation in late spermiogenesis; (3) obtained a number of new RISC-associated proteins, and found that BTG2 interacts with CAF1 and significantly promotes miRNA-induced deadenylation; (4) identified the SUMOylation of two key proteins for miRNA biogenesis in vitro and in vivo, and studied the function of such post-translational modification in miRNA biogenesis. Overall, we have fulfilled all research plans and obtained a number of important results. To date, we have published 6 research articles with the grant number in Dev Cell, Nat Commun, EMBO J, Cell Res and Immunol Lett, while several papers are under revision or review. Additionally, we have trained >20 graduate students, with 4 obtaining their Ph.D and 2 obtained their master degree. Moreover, many of them won each kind of scientific awards.%在原计划研究内容基础上，开展了piRNA、miRNA作用通路中功能蛋白质因子的筛选、功能机制研究。(1)对MIWI/piRNA机器的代谢分子机制和生理学意义进行了深入研究；(2)发现CAF1/MIWI/piRNA介导后期精子细胞中mRNA清除；(3)筛选获得了若干RISC相互作用蛋白，发现BTG2蛋白对miRNA引起的mRNA脱腺苷酸化具有显著促进作用，并且依赖于其与CAF1间的相互作用；(4)对2个与miRNA生物合成直接相关的关键蛋白质的类泛素化修饰（SUMOylation）进行了体内体外的鉴定，并进一步研究了这种蛋白质修饰的功能。该研究完成了原计划研究内容，取得了一些重要研究结果。