小核糖核蛋白复合体(snRNP)包括剪接体snRNP和U7 snRNP两类，是真核细胞中极其保守的非编码RNA-蛋白复合体。前者负责前体mRNA的剪接；后者仅负责5种组蛋白基因转录产物前体mRNA3’-端的特异性加工。它们都有一个相似的7个Sm蛋白环绕1个RNA形成的环状核心结构，并且其核心结构都由SMN复合体组装。不同的是U7 snRNP核心结构中U7 RNA和Lsm10/11蛋白取代了剪接体snRNP中的RNA和SmD1/D2。剪接体snRNP核心结构的组装已初步清楚，SMN复合体如何组装U7 snRNP核心结构却知之甚少。我们拟通过生化、结构生物学等方法研究SMN复合体中谁识别Lsm10/11和如何识别，以及U7 RNA如何特异组装进U7 snRNP复合体等基本生物学问题。本课题将揭示U7 snRNP核心结构的组装机制，解释SMN复合体同时组装两类snRNP的机制。

Small nuclear ribonucleoproteins (snRNPs), including spliceosomal snRNPs (U1, U2, U4 and U5) and U7 snRNP, are conserved and vital non-coding RNA-protein complexes in eukaryotes, playing essential roles in the pathway of genetic information transduction. The formers play major roles in splicing of pre-messenger RNAs and the latter is a key factor in the special 3’-end processing of the pre-messanger RNAs of histone genes. Both types of snRNPs share a similar core architecture consisting of 1 RNA and 7 Sm proteins which form a ring around the RNA. Their core architectures are assembled inside cells with the mediation of the SMN complex. However, spliceosomal and U7 snRNP cores are different in that the former has one of the four spliceosomal snRNAs (U1, U2, U4 and U5 snRNAs, all containing a canonical Sm site, AAUUUUUGGAG) and SmD1/D2 heterodimer whereas the latter contains a U7 snRNA (containing a special Sm site, AAUUUGUCUAG) and Lsm10/11 heterodimer in equivalent places. While the assembly mechanism of spliceosomal snRNP core mediated by the SMN complex is preliminarily uncovered, How U7 snRNP core is assembled is little known. In this proposal, we plan to study how the SMN complex recognizes Lsm10/11 heterodimer, comparing with its recognition of SmD1/D2, and how Lsm10/11 specifically directs the binding of U7 snRNA instead of splicosomal snRNAs in the assembly of U7 snRNP core at biochemical and structural levels. The completion of this proposal will reveal the mechanism of U7 snRNP core assembly mediated by the SMN complex and explain the structural basis for the difference and specificity between spliceosomal and U7 snRNP core architectures and their assemblies.