RNA编辑是在转录后水平改变RNA碱基序列的一种生物学过程。ADAR1蛋白介导双链RNA中腺嘌呤脱氨基转化成次黄嘌呤（A-to-I）的生物学反应，是人体内研究最多的一种RNA编辑方式。自从ADAR1蛋白被发现以来，ADAR1蛋白的生物学功能陆续得到揭示。有研究报道ADAR1蛋白通过调控细胞免疫水平来调控肿瘤细胞对药物的敏感性，ADAR1作为新的肿瘤药物作用靶点得到了广泛关注。也有研究报道ADAR1蛋白可以作为RNA编辑工具靶向编辑RNA，从而实现调控靶向基因的功能。ADAR1蛋白由多个结构域组成，在这些结构域的精密协作下完成识别结合RNA底物、腺嘌呤脱氨基、RNA编辑产物释放等一系列生物学反应过程。我们拟通过单颗粒冷冻电子显微学技术解析全长ADAR1蛋白以及ADAR1蛋白-RNA复合物的高分辨率三维结构，基于结构信息，结合生物化学、分子生物学等技术手段解释人源ADAR1蛋白RNA编辑机制。

RNA editing is a post-transcriptional-processing mechanism that changes the RNA sequence. In humans, ADAR1 mediated adenosine deamination to produce inosine in double strand RNA is the most studied RNA editing mode. Since the discovery of human ADAR1 protein, the biological functions of ADAR1 protein is gradually unraveled. Growing evidences show ADAR1 protein plays important roles in regulating auto-immunity and in cancer immuno-chemotherapy, which makes ADAR1 a potential target for drug development. Recent research shown ADAR1 can work as a good RNA editing tool, ADAR1 protein could precisely deaminate a specific adenosine with the guidance of designed guide RNA. ADAR1 protein is made up of multi-domains, and the collaboration of these domains has great significance in the procedure of ADAR1 recognizing RNA substrates, editing adenosine and releasing RNA products. Till now, only two domains of human ADAR1 protein have been crystalized at high resolution, which shows very limited information in explaining the editing mechanism underlying human ADAR1. Here we plan to determine the high resolution structures of human ADAR1 and ADAR1-RNA complex through cryo-EM and single particle reconstruction. Combined with the biochemistry, molecular biology and others, we will explore the RNA editing mechanism of human ADAR1.