RNA剪接是真核基因表达的主要调控机制。剪接因子的突变会导致严重的疾病，包括脊髓肌肉萎缩症(SMA)，视网膜色素变性(RP)等。目前，对许多剪接因子的功能和突变致病的分子机制了解非常有限。利用我们建立的研究线虫体内RNA剪接的遗传学工具，最近我们发现SMA和RP的相关致病基因smn-1和prp-8,以及一个抑癌剪接因子相关基因T08B2.5都和剪接因子U2AF大亚基基因uaf-1相互作用，为研究这些基因的体内功能提供了新的切入点。为了深入了解smn-1, prp-8和T08B2.5如何调控RNA剪接，我们计划研究smn-1和uaf-1相互作用的分子机制，鉴定prp-8和T08B2.5的遗传突变，阐明这些突变如何影响uaf-1的功能，最后探索smn-1,prp-8和T08B2.5之间可能存在的相互作用关系。通过这些工作，我们希望进一步认识这些剪接因子的体内功能和相关疾病的可能发病机理。

RNA splicing is a fundamental regulatory mechanism for eukaryotic gene expression. Mutations in RNA splicing factors could lead to severe diseases, which include spinal muscular atrophy (SMA) and retinitis pigmentosa (RP). It remains to be understood about how these splicing factors function in vivo and why mutations in these factors cause diseases. Using genetic tools we established for studying the in vivo regulation of RNA splicing, we found that the C. elegans SMA-related gene smn-1, RP-related gene prp-8 and a tumor suppressor-related gene T08B2.5 all interact with the U2AF large subunit gene uaf-1, providing new approaches for studying the in vivo functions of these genes. To further understand how these genes function, we propose to identify the molecular mechanism underlying the interaction of smn-1 and uaf-1, characterize the genetic mutations of prp-8 and T08B2.5, investigate how prp-8 and T08B2.5 affect the function of uaf-1, and identify possible interactions of smn-1, prp-8 and T08B2.5. We hope our studies will provide novel understandings about the in vivo functions of these genes and insights into the molecular mechanisms of related diseases.