纤毛相关激酶受RNA编辑调控的机理研究

MAP激酶DYF-5在纤毛的形成和维持过程中发挥着重要作用，然而，它发挥功能的机制仍不清楚。申请人拟采用秀丽隐杆线虫的感觉纤毛为研究对象，结合体外培养哺乳细胞体系，系统解析DYF-5激酶的作用机理。申请人的初步结果表明：DYF-5激酶的活化（DYF-5CA），能够导致纤毛结构和功能的异常；通过正向遗传筛选，鉴定RNA编辑酶ADR-2会对DYF-5CA pre-mRNA的碱基进行编辑，进而影响正常蛋白的产生。以此为基础，本项目拟综合运用遗传学、分子生物学、生物信息学等多种方法进一步揭示并完善纤毛相关激酶受RNA编辑调控的作用机制，为纤毛结构和功能异常所导致的人类疾病的生理和病理机制研究提供理论基础。

MAP kinase DYF-5 plays an important role in the formation and maintenance of cilia, however, the mechanism is still unclear. We aim to use the sensory cilia of Caenorhabditis elegans as our experimental system, combined with the in vitro cultured mammalian cell system, to systematically analyze the mechanism of DYF-5 kinase. The applicant’s preliminary results show that: the activation of DYF-5 kinase (DYF-5CA) can lead to abnormalities in the structure and function of cilia; through forward genetic screening, it was identified that the RNA editing enzyme ADR-2 would affect DYF-5CA pre-mRNA. The bases are edited, which in turn affects the production of normal proteins. Based on this, this project intends to comprehensively use genetics, molecular biology, bioinformatics and other methods to further reveal and improve the mechanism of cilia-related kinases regulated by RNA editing, thus provides a theoretical basis of human diseases caused by abnormal cilia structure and function.