微RNA关键结合蛋白的功能与机制研究

刘默芳

摘 要：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。

关键词：piRNA PIWI miRNA RISC 翻译后修饰

Abstract： 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.

Key Words： PiRNA； PIWI； MiRNA； RISC； Post-translational modification

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