在抗病毒固有免疫反应中发挥调控作用的环状RNA的筛选及功能机制研究

RNA病毒感染会诱导宿主一系列应答基因的表达改变，实现对抗病毒免疫强度的精密调控，circRNAs在这一领域的作用近几年初露头角,但关键circRNAs的鉴定和功能机制研究还有很多未知领域。本申请在课题组多年研究基础上，通过circRNA芯片筛选RNA病毒感染后差异表达circRNAs。在前期已经验证差异表达基础上，通过过表达、基因敲低、基因敲除等技术手段探讨关键circRNAs在抗病毒应答中的调控作用；利用双荧光素酶报告系统、RIP、RNA pull-down等探讨circRNAs发挥作用的具体机制；利用circRNA基因敲除小鼠检测其对抗病毒免疫的作用。以期对细胞质RNA病毒感受器相关信号调控的差异circRNAs有较一整体认识，并对关键的circRNAs所发挥的调控作用及机理进行深入探讨，拓展circRNA在抗病毒固有免疫反应中作用的理论认识，并为相关疾病的干预提供了新的靶标。

RNA virus infection induces the expression pattern changes of a series of response genes in the host to achieve the precise regulation of the immune strength against the virus. The role of circRNAs in antiviral immunity has been emphasized in recent years. However, there are still many unknown areas for the identification and functional mechanism research of key circRNAs in innate immunity. Based on years of research of our group, circRNA chip was used to screen the differential expression of circRNAs upon RNA virus infection. On the basis of verified differential expression of circRNAs, the regulatory roles of key circRNAs in antiviral response were investigated by means of overexpression, gene knockdown and gene knockout. The specific mechanism of the role of circRNAs was investigated by using the dual luciferase reporting system, RIP, RNA pull-down, etc. CircRNA knockout mice were used to monitor the anti-virus immunity. This study helps to have a more comprehensive understanding of differential circRNAs regulated by cytosolic RNA sensor mediated signal, to further explore the regulatory roles and mechanism of key circRNAs, and to expand the theoretical understanding of the roles of circRNAs in antiviral innate immune response, and provide new targets for the intervention of related diseases.