微RNA關(guān)鍵結(jié)合蛋白的功能與機(jī)制研究

劉默芳

摘 要：在原計(jì)劃研究內(nèi)容基礎(chǔ)上，開展了piRNA、miRNA作用通路中功能蛋白質(zhì)因子的篩選、功能機(jī)制研究。（1）對MIWI/piRNA機(jī)器的代謝分子機(jī)制和生理學(xué)意義進(jìn)行了深入研究；（2）發(fā)現(xiàn)CAF1/MIWI/piRNA介導(dǎo)后期精子細(xì)胞中mRNA清除；（3）篩選獲得了若干RISC相互作用蛋白，發(fā)現(xiàn)BTG2蛋白對miRNA引起的mRNA脫腺苷酸化具有顯著促進(jìn)作用，并且依賴于其與CAF1間的相互作用；（4）對2個(gè)與miRNA生物合成直接相關(guān)的關(guān)鍵蛋白質(zhì)的類泛素化修飾（SUMOylation）進(jìn)行了體內(nèi)體外的鑒定，并進(jìn)一步研究了這種蛋白質(zhì)修飾的功能。該研究完成了原計(jì)劃研究內(nèi)容，取得了一些重要研究結(jié)果。

關(guān)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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