蛋白质精氨酸甲基转移酶5（PRMT5），参与表观遗传调控、DNA修复、细胞死亡等过程。选择性剪接(AS)，是指在mRNA前体中剪切掉不同内含子或外显子后以不同组合方式产生成熟mRNA的过程，是蛋白质多样化的主要来源。我们发现，辐射作用于细胞株和肝癌患者后PRMT5发生了AS过程（出现ISO1、2和5剪接子），有关机制研究尚未见报道。本研究首先确定PRMT5的AS过程与辐射敏感性有关，进而分别从不同功能结构域（启动子、剪接增强子和沉默子、内含子CU多嘧啶区和G束区）、剪接体形成过程（外显子识别、内含子识别、RNA聚合酶II延伸）、表观遗传（DNA甲基化、翻译后修饰、反义LcnRNA）对PRMT5发生AS的机制进行探讨，最后通过整体研究（动物实验、患者监测与随访分析）揭示PRMT5的AS机制与肝癌发生及放疗预后的相关性。本研究将丰富辐射损伤中有关AS作用的理论并对临床放射诊疗具有指导意义。

Protein arginine methyltransferase 5(PRMT5) could participate in the process of epigenetic regulation, DNA repair, cell death, etc. Alternative splicing means that the introns and the selective extrons are spliced from the pre-mRNA and the remaining extrons are linked together to form different transcripts, consequently creat much more proteins than we could predict according as the amounts of genes. We have found that after the treatment of radiation different splicers of PRMT5 appeared in cell lines and patients with hepatocarcinoma, i.e., PRMT5-ISO 1, 2 and 5, while the relative mechanisms are still unclear. In this study, (1) we will firstly clarify the occurrence of the alternative splicing of PRMT5 and its relationship with radiation-induced cell death. (2) Then different aspects will be chosen for the studies of underlying mechanisms, one is the functional structure domains such as promoter, the UC-rich tract and G tract in the intron, extron splicing enhancer(ESE)/Intron splicing enhancer(ISE), Extron splicing silencer(ESS)/Intron splicing silencer(ISS); the next is the formation of splicesomes, including extron recognization/definition, intron recognization/definition, RNA polymerase II elongation; furthermore, the epigenetic regulation including DNA methylation, post-transcriptional modification, anti sense-LncRNA, will be clarified; (3) Finally in vivo studies will be used for the observation of the effects of AS regulation on hepatocarcinoma development, radiosensitivity and the prognosis, the xenograft models of null mice and the patients with hepatocarcinoma receiving ionizing radiation treatment will be detected. As a whole, this study will definitely fulfill the regulation mechanisms of alternative splicing and show promising prospect in guiding radiation oncology.