选择性剪接可使一个基因产生具有不同功能的蛋白异构体。在正常条件下，选择性剪接的调控是受到严格控制的，选择性剪接的异常可导致包括癌症在内的许多疾病。我们的前期研究发现CD46基因Exon13在肾癌中存在异常的可变剪接，其中CD46-exon13+(CD46-CYT1)在肾癌中高表达，而CD46-exon13-(CD46-CYT2)在肾癌中低表达。我们还发现SFPQ可调节CD46的可变剪接。我们通过一系列体内和体外实验证实CD46-CYT1在肾癌发生发展中起着促癌基因的作用。此外，我们通过亲和纯化-质谱等技术证实MAT2A可特异地与CD46-CYT1相互作用。在此基础上，本课题拟通过一系列体内和体外实验研究SFPQ/CD46/MAT2A剪接调控网络在肾癌发生发展中的作用机制，并为肾癌的诊断和治疗提供新的理论依据和药物靶点。

Alternative splicing enables one gene to produce multiple protein isoforms with different functions. Under normal conditions, this mechanism is tightly regulated. When deregulated, the aberrant splicing mRNA could cause many kinds of diseases including cancer. Here, we identified inclusion of CD46 exon 13 (CD46-CYT1) was greatly promoted in human renal cancer tissues. We further showed that alternative splicing of CD46 pre-mRNA is regulated by SFPQ. Our evidences showed that CD46-CYT1 acts as an oncogene in renal carcinoma. To better understand the cellular function of CD46, here we have isolated and identified cellular CD46 CYT1 domain or CYT2 domain binding partners using TAP-tag purification and MS identification. Further co-immunoprecipitation experiments confirmed the binding between MAT2A and CD46-CYT1. In this project, we plan to systematically study the function and the molecular mechanism of SFPQ/CD46/MAT2A interaction in renal cancer development and progression by a variety of in vitro and in vivo assays, and which will benefit the diagnosis and treatment of ccRCC.