Regulation of Alternatiive Cleavage and Polyadenylation

项目总结 大多数哺乳动物基因都有多个切割和多聚腺苷酸化(C/P)位点，或PAS，导致 具有不同编码序列(CDS)和/或3‘非翻译区(3’UTRs)的mRNA异构体。 选择性切割和多聚腺苷酸化(APA)被认为是一种重要的基因层 调节，影响蛋白质多样性和信使核糖核酸代谢。不同基因的APA模式有所不同 细胞/组织类型，并在不同条件下动态调节，例如增殖， 分化，并对细胞外提示做出反应。然而，APA的机制并不完善。 明白了。我们的长期目标是了解APA在不同细胞/组织中的“调控密码” 在生理和病理条件下及其生物学后果。在这项提案中，我们 有三个具体目标：第一，我们将研究C/P因素在APA调控中的作用。第二，我们 将研究C/P基因是如何受APA调控的。第三，我们将研究两者之间的相互作用 核出口和APA。我们预计这笔拨款的结果将提供关于 APA的机制，阐明其在不同细胞和组织中的意义以及 发展与差异化。

PROJECT SUMMARY Most mammalian genes have multiple cleavage and polyadenylation (C/P) sites, or pAs, resulting in mRNA isoforms with different coding sequences (CDS) and/or 3' untranslated regions (3'UTRs). Alternative cleavage and polyadenylation (APA) is rapidly recognized as an important layer of gene regulation, affecting protein diversity and mRNA metabolism. The APA pattern of genes varies across cell/tissue types and is dynamically regulated under different conditions, such as proliferation, differentiation, and in response to extracellular cues. The mechanisms of APA, however, are poorly understood. Our long-term goal is to understand the `regulatory code' of APA in different cells/tissues under physiological and pathological conditions and its biological consequences. In this proposal, we have three specific aims: First, we will examine the role of C/P factors in APA regulation. Second, we will examine how C/P genes are regulated by APA. Third, we will examine the interplay between nuclear export and APA. We expect that the result of this grant will provide systematic views on the mechanisms of APA and shed light on its significance in different cells and tissues, as well as development and differentiation.