Pre-mRNA的可变剪接是增加基因组多样性和调控转录后基因表达的重要机制。近些年，一些研究结果显示可变剪接能够应答细胞信号。然而，我们对这些信号是如何被传递到剪接机器从而调控可变剪接的机制以及它们调控可变剪接功能的认识还非常有限。在本项研究中，我们将以EGF信号通路为模型，运用生物化学、细胞生物学、分子生物学、生物信息学等方法，围绕RNA结合蛋白hnRNP A1泛素化修饰在EGF信号通路中的机制与功能开展研究。我们将重点研究EGF信号诱导hnRNP A1泛素化的机制，确定泛素化修饰对hnRNP A1活性与功能的影响，并探索EGF信号通过hnRNP A1泛素化调控可变剪接的功能、机制与作用途径。通过本项研究，我们期望能够增加对细胞信号调控可变剪接机制的理解，为与肿瘤发生密切相关的EGF信号通路提供新的作用途径，并开启认识RNA结合蛋白泛素化修饰在发育与疾病中调控功能的研究。

Pre-mRNA alternative splicing is an important mechanism that plays a critical role in increasing genome diversity and regulating gene expression at post-transcriptional level. Recent studies have shown that alternative splicing is subject to cellular signals. However, how signals are transmitted to splicing machinery to affect alternative splicing and what are the functions of signal-induced splicing regulation remain elusive. In this study, using EGF signal pathway as a model, we will apply biochemical, cell biological, molecular biological, and bioinformatics approaches to understand the functions and mechanisms of hnRNP A1 ubiquitination in EGF signaling. We will focus on identifying the mechanisms by which EGF induces hnRNP A1 ubiquitination, characterizing the effects of ubiquitination on the activity and function of hnRNP A1, and investigating the functions, mechanisms, and pathways of hnRNP A1 ubiquitination-mediated alternative splicing in EGF signaling. Taken together, we aim to increase our understanding on the mechanisms of signal-induced splicing regulation, provide new insights into the cancer-related EGF signal pathway, and open new doors to understand the regulation of RNA binding proteins in development and disease.