参与基因表达转录后调控的重要蛋白质-RNA复合物的结构与功能研究

转录后调控是真核生物基因表达在RNA水平上的调控，影响细胞的生长与分化。转录后调控主要通过RNA结合蛋白（RBPs）直接或间接地与mRNA相互作用来完成基因表达调控的。本项目拟选取参与转录后调控的重要蛋白质-RNA复合物，包括SHE复合物及WD40重复蛋白，如Gemin5、Brat和Wdr33与RNA之间形成的蛋白质-RNA复合物为研究对象，通过X-射线晶体学手段解析这些蛋白质-RNA复合物的三维晶体结构。根据结构分析，寻找蛋白质-RNA相互作用的关键位点，并结合功能实验研究这些蛋白质特异识别RNA的分子机制以及它们在基因表达转录后调控过程中所起的作用。同时，该项工作将揭示WD40结构域识别不同RNA的共同特性，并由此推广出WD40结构域与RNA相互作用的普遍模式。

Post-transcriptional regulation is the control of gene expression at RNA level in eukaryotes, that impacts cell growth and differentiation. RNA binding proteins (RBPs) play important roles in this regulation by interacting with mRNA directly or consequentially. This project aimed to study the structure and function of important protein-RNA complexes during post-transcriptional control, including SHE complex and WD40 repeat proteins, like Gemin5, Brat and Wdr33, interacting with RNAs. Using X-ray crystallography, we will determine the 3D crystal structures of these protein-RNA complexes. Based on structural analysis, we plan to identify sites important for interaction between these proteins and RNAs. By functional studies, we will investigate the molecular mechanisms of recognition between these proteins and RNAs and how they function in post-transcriptional gene regulation. Furthermore, this work will be useful for delineating the common feature of WD40 domain in recognizing different RNAs, and extend the knowledge of the interaction mode between WD40 domain proteins and RNAs.