Structural characterization of U11 snRNP complex

Minor spliceosome is responsible for removal of a rare class of introns that are present in many essential genes. Despite its fundamental importance, much information remains elusive for a comprehensive understanding of minor spliceosome assembly and molecular basis of the diseases associated with its malfunctions in human. My project focuses on the study of U11/U12 di-snRNP. Our goal is to solve its structure and to investigate how minor introns are recognized. By applying single particle cryo-electron microscopy (cryo-EM) and proteomics, we will reveal the spatial organization and composition of the U11/U12 di-snRNP. These results will help us to understand how major and minor introns are distinguished by different machinery inside human.次要剪接体（minor spliceosome）负责催化切除存在于众多必需基因中的一类稀有内含子。尽管其具备核心生物学功能，但目前学界对次要剪接体的组装机制，以及其功能异常所关联的人类疾病的分子基础，仍缺乏全面的认知。本项目聚焦于U11/U12双小核核糖核蛋白（U11/U12 di-snRNP）的研究，旨在解析其三维结构，并阐明稀有内含子的识别机制。本研究将采用单粒子冷冻电子显微镜（cryo-EM）与蛋白质组学技术，揭示U11/U12双小核核糖核蛋白的空间排布与组分组成。上述研究结果将有助于阐明人类细胞内不同剪接机器如何区分识别主要内含子与稀有内含子。