新型RNA修饰的检测技术开发与功能研究

RNA modification refers to various types of modifications occurring on RNAs. As a class of gene regulation manner which only receives broad notifications until recently, RNA modification has been proven to play important roles in many physiological and pathological processes. However, the research on RNA modifications is still at its early stage worldwide, there are many blank spots need to be filled in terms of the detection methods of RNA modifications, regulatory proteins for RNA modification and biological functions of RNA modifications. Basing on the foundation laid by previous work, this project will focuse on the major types of RNA methylation modifications, namely m6A, m6Am, m5C and m7G modifications, targeting the key obstacles related to these modifications, to develop novel RNA modification detection methods with high resolution, high specificity, and low sample amount requirement, to identify key regulators and binding proteins for these modifications, and to study the functions of these modifications in regulating memory and other neurological activities, as well as host anti-virus immune responses. The application team contains the leading scientists in RNA modification research field with strong relevant research background, has received support of previous projects from this program and has published over 40 research papers related to RNA modifications on the top-class research journals, such as Nature. With the support of this project, there is a great chance for the application team to achieve more leading discoveries.

RNA修饰是指发生在RNA上的各种修饰形式。作为一类新近才受到普遍关注的基因调控方式，RNA修饰已经被证明在多种生理病理过程中发挥重要的作用。但目前国际上对于RNA修饰的研究还处于刚刚起步的阶段，在RNA修饰的检测技术、相关调控蛋白和生物学功能等方面均存在很多空白。基于前期研究基础，本项目将围绕m6A、m6Am、m5C和m7G这几种重要的RNA甲基化修饰类型，针对目前国际上在这几种修饰的研究中面临的共性关键问题，重点开展高精度、高特异性、低样本量的RNA修饰的检测方法开发，RNA修饰关键调控和结合蛋白鉴定，和RNA修饰在记忆等神经系统活动与宿主抗病毒免疫应答等方面的功能研究。项目申请团队依托本重大研究计划的前期支持，整合了我国RNA修饰领域的优势研究力量，具有较强的相关研究基础，曾在Nature等国际一流学术期刊发表RNA修饰相关的研究论文40余篇，有望在项目的支持下取得更多引领性成果。

项目围绕既定目标开展研究，在新的RNA甲基化修饰检测方法开发、RNA甲基化相关数据分析方法开发、RNA 甲基化相关蛋白发现、和RNA 甲基化相关的功能研究方面均取得较好成果。开发了针对任务书规定的m6A、m6Am、m5C修饰相关的具备单细胞或单碱基分辨率等技术优势的新检测技术6项，还开发了针对2'-O-Me修饰、假尿嘧啶修饰等项目书没有包含的RNA修饰类型检测方法4项，开发了Pol3Base、RMBase、tsRFun、ChIPBase、colorCells、deepBase、COSG、SimCH等RNA修饰相关的数据资源库与软件7项，发现了RNA m5C修饰新的结合蛋白YBX2，解析了m6A、m5C等RNA修饰在小鼠胚胎发育、动脉粥样硬化、细胞再生、新冠病毒感染和免疫调控等方面的功能与作用机制。项目产出已发表或已接收研究论文47篇，还有1篇论文在修回中。项目申请专利5项，获得授权专利2项。项目在人才培养方面也取得突出成果。项目团队成员多次获得各种奖励，杨建华在执行期获得基金委国家杰出青年科学基金的资助，杨莹入选2022年度科睿唯安“高被引学者”。在本项目资助下，共培养博士研究生12名，硕士研究生5名，博士后出站人员1名。项目建立多个RNA数据分析相关网站，单日总使用量超过5000次，在服务科研人员方面取得较好效果。