m6A读码器的系统鉴定及功能机制研究

m6A修饰是真核细胞mRNA中最高丰度的RNA修饰类型，与具有特定识别结构域的读码器(reader)互作调控着mRNA的功能与命运。虽然已有成千上万的m6A修饰位点被鉴定，但是否存在其它的RNA结合蛋白(RBP)去识别m6A修饰并发挥功能仍有待阐明。我们前期建立了多维高通量的RNA结合蛋白靶标组(RBPome)分析体系，发现了一批潜在的m6A修饰结合蛋白。在此基础上，本项目拟采用实验与生物信息学相结合的方法，开发基于表观转录组和RBPome数据发掘m6A读码器及其调控网络的新算法和技术，系统地研究和解析多个m6A读码器的功能及其介导的表观调控机制。本研究将有助于揭示m6A读码器对RNA的生成代谢、RNA-蛋白质复合物的功能及其在细胞活动中的重要作用，并为肿瘤等疾病研究提供新的潜在靶标。

N6-methyladenosine (m6A) is the most prevalent modification in eukaryotic messenger RNAs (mRNAs) and is interpreted by its readers with specific domain-containing proteins, to regulate the mRNA fate. Although high-throughput sequencing has identified thousands of m6A sites, whether they can be recognized by other RNA-binding proteins remains unknown. In our previous studies, we have developed the bioinformatic pipeline RBPome to identify the m6A readers. In the present project, we will develop new algorithms and technology platforms based on integration of epitranscriptomic and RBPomic data to systematically identify novel m6A readers and their regulatory networks. We will further investigate the effects of m6A readers on physiological processes and explore their potential roles in epigenetic regulation mechanisms. The studies proposed here will provide new insights into the regulatory rules of m6A readers in RNA biogenesis, metabolism, and biological functions of ribonucleoprotein complexes (RNPs). Our study will also provide new potential targets for cancer therapy.