核内小核糖核苷酸（snRNA）是剪接体复合物的重要组成部分，它与Sm蛋白组装成snRNP后参与识别并剪切pre-mRNA，从而调控真核细胞中基因的表达；一旦该过程发生异常，便会导致脊髓性肌萎缩症、慢性白血病和癌症等严重的疾病表型。为保证其发挥正常功能，snRNA的成熟与修饰过程需要受到运动神经元生存蛋白质复合物（SMN complex）的严谨调控，但是其作用机制目前仍尚不清楚。为了了解SMN正确识别snRNA和Sm蛋白并指导snRNP正确组装的具体机制，我们在哺乳细胞表达系统中表达并通过两步亲和纯化的方法得到了SMN复合物特定中间状态的蛋白复合物。本项目旨在通过利用单颗粒冷冻电镜技术，解析特定阶段SMN复合物的三维蛋白结构并揭示SMN指导snRNP分步逐级组装的分子机制。本项目将进一步加深人们对细胞中的RNA成熟和质量控制机制的理解，为探究相关疾病的发生机制和药物研发提供基础支持。

As the most important components of spliceosome, snRNAs recognizing and splicing pre-mRNA to control the selective expression of specific genes in cells; abnormality of snRNAs would lead to server diseases such as SMA、AML、cancer et. During its maturation, the pre-snRNA needs to be recognized and recuited by SMN complex, then assemblied with Sm proteins to form the fuctional snRNP. However，the accuracy mechanism of snRNP assembly still unclear for now. To elucidate how SMN complex recognize snRNA and Sm proteins, and guide the subsequented assembly of snRNP, we purified SMN complex from mammalian cells by using two-way affinity purification. This project aims to reveal the structural basis of SMN complex and elucidate how SMN complex guide the step-wise assembly of snRNP. Results of this project will expand current understanding of the process of RNA maturation and quality control, and provide fundamental support for studying the cause of related diseases.