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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