RBM25介导的选择性剪接在心力衰竭发病机制中的作用

本研究前期发现心力衰竭（HF）时RBM25mRNA及其蛋白表达增多，且增多的RBM25和Luc7A一起介导了钠通道SCN5A mRNA的异常剪接，这促进了HF的发展，同时我们发现RBM25增多时USF2、P53也表达增多，据此提出假说：RBM25通过调节USF2的前体RNA可变剪接来调控USF2的表达，进而通过作用于P53来调控细胞凋亡。为验证假说我们拟通过构造心肌细胞心衰模型、小鼠心衰模型，用慢病毒转染系统来控制RBM25的表达。研究RBM25调控细胞凋亡的分子通路，阐明RBM25与USF2之间的作用机制，为HF患者提供新的治疗靶点。

Early our studides have found that RBM25mRNA and its protein expression increased in heart failure (HF), In addition, RMB25 and Luc7a together mediate the abnormal splicing of SCN5A mRNA in sodium channel, which promoted the development of HF. At the same time, we found that the expression of USF2 and P53 increased with the increase of RBM25. Based on this, the hypothesis is put forward: RBM25 regulates the expression of USF2 by regulating the variable splicing of USF2 precursor RNA, and then regulates apoptosis by acting on P53. In order to test the hypothesis, we intend to control the expression of RBM25 by entiviral transfection in heart failure model of cardiomyocytes and mice.To study the molecular pathway of RBM25 regulating cell apoptosis, elucidate the mechanism between RBM25 and USF2, and provide a new therapeutic target for HF patients.