Regulation of alternative cleavage and polyadenylation

项目总结 大多数哺乳动物的基因含有多个切割和多聚腺苷酸化位点，或PASS，从而导致信使核糖核酸 具有不同编码序列(CDS)和/或3‘非翻译区(3’UTRs)的异构体。备择 切割和多聚腺苷酸化(APA)被迅速认识到是基因调控的重要一层，影响 基因表达、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，在增殖、分化和发育过程中受到动态调节，并在 对细胞外暗示的反应。然而，人们对APA的作用机制知之甚少。我们的长期合作 目的是了解APA在不同细胞/组织中的调节密码 病理情况。在这项建议中，我们有三个具体目标：第一，我们将系统地研究一个 APA法规中的终止因素集。第二，我们将研究3‘端之间的相互作用 APA法规中的加工和拼接。第三，我们将开发一种改变APA的基因组方法。我们 预计这笔赠款的结果将使人们全面了解《行政程序法》和《行政程序法》的机制 通过APA调节基因表达的工具。

PROJECT SUMMARY Most mammalian genes harbor multiple cleavage and polyadenylation sites, or PASs, 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 gene expression, protein diversity and mRNA metabolism. The APA pattern of genes varies across cell/tissue types, is dynamically regulated in proliferation, differentiation and development, and alters 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. In this proposal, we have three specific aims: First, we will systematically examine a set of termination factors in APA regulation. Second, we will examine the interplay between 3’ end processing and splicing in APA regulation. Third, we will develop a genomic method to alter APA. We expect that the result of this grant will provide comprehensive understanding of the mechanisms of APA and tools to regulate gene expression through APA.