Regulation of alternative cleavage and polyadenylation

选择性切割和聚腺苷酸化的调控

基本信息

批准号：
10409815
负责人：
BIN TIAN
金额：
$ 46.92万
依托单位：
WISTAR INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-05-01 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10409815
关键词：
3&apos Untranslated Regions Abbreviations Address Affect Alternative Splicing Bioinformatics Biological Assay C-terminal CRISPR/Cas technology Cell Proliferation Cells Clustered Regularly Interspaced Short Palindromic Repeats Code Coupled Cues DNA Polymerase II DNA-Directed RNA Polymerase Development Distal Engineering Exons Gene Expression Gene Expression Regulation Genes Genetic Transcription Genomics Goals Grant Human Human Cell Line Introns Light Messenger RNA Metabolism Methods Molecular Biology Names Pathologic Pattern Phosphorylation Physiological Play Poly A Polyadenylation Protein Isoforms Proteins RNA Splicing Regulation Reporter Reporting Role Site Stress System Techniques Tissues Transcript U1 Small Nuclear Ribonucleoprotein U2 Small Nuclear Ribonucleoprotein base cell type extracellular innovation knock-down mRNA Cleavage and Polyadenylation Factors neurogenesis novel overexpression response termination factor tool transcription termination

项目摘要

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.

项目摘要大多数哺乳动物基因都具有多个裂解和聚腺苷酸位点，或通过，导致mRNA 具有不同编码序列（CD）和/或3'未翻译区域（3'UTRS）的同工型。选择裂解和聚腺苷酸化（APA）迅速被认为是基因调节的重要层，影响了基因表达，蛋白质多样性和mRNA代谢。基因的APA模式各不相同细胞/组织类型在增殖，分化和发育中动态调节，并在改变对细胞外提示的反应。但是，APA的机制知之甚少。我们的长期目标是了解生理和生理和病理状况。在此提案中，我们有三个具体的目标：首先，我们将系统地检查 APA调节中的一组终止因子。其次，我们将检查3'端之间的相互作用 APA调节中的处理和剪接。第三，我们将开发一种基因组方法来改变APA。我们期望这笔赠款的结果将提供对APA机制和通过APA调节基因表达的工具。