微RNA關鍵結合蛋白的功能與機制研究

劉默芳

摘 要：在原計劃研究內容基礎上，開展了piRNA、miRNA作用通路中功能蛋白質因子的篩選、功能機制研究。（1）對MIWI/piRNA機器的代謝分子機制和生理學意義進行了深入研究；（2）發現CAF1/MIWI/piRNA介導后期精子細胞中mRNA清除；（3）篩選獲得了若干RISC相互作用蛋白，發現BTG2蛋白對miRNA引起的mRNA脫腺苷酸化具有顯著促進作用，并且依賴于其與CAF1間的相互作用；（4）對2個與miRNA生物合成直接相關的關鍵蛋白質的類泛素化修飾（SUMOylation）進行了體內體外的鑒定，并進一步研究了這種蛋白質修飾的功能。該研究完成了原計劃研究內容，取得了一些重要研究結果。

關鍵詞：piRNA PIWI miRNA RISC 翻譯后修飾

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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