Mechanisms and regulation of mRNA 3' processing

项目概要： 我的研究计划的长期目标是详细了解 哺乳动物mRNA的3'加工及其调控。mRNA 3 '-末端形成，通常 包括内切核酸裂解，然后是多腺苷酸化，是一个重要步骤， 真核生物基因表达，它显著影响RNA代谢的许多方面， 包括mRNA稳定性、亚细胞定位和翻译。此外，大多数 的真核基因产生多种具有不同3'末端的mRNA同种型， 交替多聚腺苷酸化（阿帕）。最近的研究表明，阿帕是高度 在发育过程中受到调控，并在转录后基因中起重要作用 调控异常的阿帕模式与多种疾病有关， 从癌症到神经系统疾病mRNA中的关键未决问题3' 处理领域包括：1）mRNA 3'端的结构与功能关系是什么 处理复合体; 2）mRNA 3'加工如何受细胞信号传导调节; 3）mRNA 3'加工如何受细胞信号传导调节。 阿帕受RNA结合蛋白的调控？我们将通过使用 生物化学、结构和基因组分析。这些研究的结果不仅 为真核基因表达中的这一关键步骤提供了新的见解，也为基因表达的研究铺平了道路。 为许多疾病开发新疗法的方法。

Project summary: The long-term goal of my research program is to understand, in detail, the mechanisms of mammalian mRNA 3’ processing and its regulation. mRNA 3’-end formation, typically involving an endonucleolytic cleavage followed by polyadenylation, is an essential step of eukaryotic gene expression and it significantly impacts many aspects of RNA metabolism, including mRNA stability, subcellular localization and translation. In addition, the majority of eukaryotic genes produce multiple mRNA isoforms with distinct 3’ ends through alternative polyadenylation (APA). Recent studies have revealed that APA is highly regulated in development and plays an important role in post-transcriptional gene regulation. Aberrant APA patterns have been associated with a wide range of diseases, from cancer to neurological disorders. Key outstanding questions in the mRNA 3’ processing field include: 1) what is the structure-function relationship of the mRNA 3’ processing complex; 2) how is mRNA 3’ processing regulated by cell signaling; 3) how is APA regulated by RNA-binding proteins? We will address these questions by using biochemical, structural, and genomic analyses. The results of these studies will not only provide novel insights into this key step in eukaryotic gene expression, but also pave the way for developing novel therapy for many diseases.