m6A识别蛋白FIP1L1在mRNA 3'末端加工的功能机制研究

m6A修饰是真核细胞mRNA上最高丰度最保守的表观遗传修饰，通过招募m6A读码器（reader）共同调控mRNA的命运与功能。虽然成千上万的m6A修饰位点已经被发现是位于3’非翻译区(3’-UTR)，但是是否存在新的m6A读码器识别这些m6A修饰位点参与调控mRNA前体（pre-mRNA）的3’末端加工亟待阐明。我们前期通过建立RNA结合蛋白靶标组分析体系，发现一批潜在的参与mRNA剪接的m6A结合蛋白，并用实验证实FIP1L1蛋白为新的m6A读码器。在此基础上，我们将开发鉴定全长RNA分子的高通量测序技术并联合多组学测序方法和功能实验方法，在转录组层面系统解析新的m6A读码器FIP1L1依赖m6A修饰调控pre-mRNA 3’末端加工的分子机制，揭示m6A修饰新的调控功能，并为RNA加工与代谢研究提供新的技术与思路。

N6-methyladenosine (m6A) is the most abundant and conserved epitranscriptomic modification on eukaryotic mRNA, which regulates mRNA fate and function by recruiting m6A readers. Although thousands of m6A sites have been found in the 3’ untranslated region (3’-UTR), it remains to be clarified whether there are unknown m6A readers that identify these m6A sites in the 3’-UTR and are involved in the regulation of pre-mRNA 3’-end processing. In our previous work, through the establishment of the RNA-binding protein targetome analysis system, we found a batch of potential m6A binding proteins involved in mRNA splicing and confirmed FIP1L1 protein as a novel m6A reader by experiments. Based on these, we will develop high-throughput full-length RNA sequencing technology and integrate multi-omics sequencing methods, as well as functional methods, to systemically clarify the molecular mechanism of m6A reader FIP1L1 which is dependent on m6A to regulate the pre-mRNA 3’end processing at the transcriptome level. Our project will reveal the novel regulatory function of m6A modification and provide new technologies and insights in the field of RNA processing and metabolism.