MOLECULAR ANALYSIS OF BASAL TRANSCRIPTION FACTOR SNAPC

基础转录因子 SNAPC 的分子分析

• 批准号: 6285077
• 负责人: Ronald William HENRY
• 金额: $ 18.55万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6285077
• 关键词: DNA binding protein; DNA directed RNA polymerase; binding proteins; eukaryote; gene expression; genetic mapping; genetic regulation; genetic transcription; human genetic material tag; immunoprecipitation; laboratory rabbit; monoclonal antibody; phosphorylation; protein protein interaction; retinoblastoma; small nuclear RNA; transcription factor

DESCRIPTION (adapted from applicant's abstract): Transcriptional regulation involves an interplay between regulatory proteins and the general transcriptional machinery and is a key mechanism for control of many biological processes. Coordination of gene expression is critical for healthy development, differentiation, immune responses, and the maintenance of cellular homeostasis. Disruptions in the program of transcriptional regulation are observed in many diseased states such as cancer. Therefore, it is important to develop an understanding of fundamental transcriptional mechanisms. The long-term objective of this study is to understand how eukaryotic basal transcription factors function in transcription and gene regulation. The model system that the principal investigator uses is the transcription of human small nuclear (sn) RNA genes. The snRNA gene family represents a large collection of genes that have important functions in the cell. These genes have similar promoter architectures and yet RNA polymerase II transcribes some of these genes while RNA polymerase III transcribes others. Thus, these genes offer a powerful system to analyze the molecular mechanisms of transcription for both RNA polymerase II and III. Transcription of human snRNA genes, regardless of polymerase specificity, requires the basal transcription factor referred to as snRNA activating protein complex (SNAPc). This multi-protein complex binds specifically to the core-promoter regions of human snRNA genes. SNAPc is composed of at least five proteins SNAP 19, SNAP43, SNAP45, SNAP5O, and SNAP 190. In addition, the TATA-box binding protein (TBP) co-purifies with SNAPc. Each of these proteins is required for snRNA transcription by both RNA polymerases II and III. These proteins also contribute to the regulated transcription of human snRNA genes. Human U6 gene transcription by RNA polymerase III is repressed by the retinoblastoma tumor suppressor protein (Rb) and this may involve communication between Rb and SNAPc. The principal investigator has chosen to study SNAPc because this complex plays a key role in human snRNA gene transcription by both RNA polymerases II and III and is a direct target of regulatory proteins such as Rb. This project will employ molecular techniques to understand the function of individual members of SNAPc for regulated transcription by RNA polymerases II and III.

描述（根据申请人的摘要改编）：转录法规 涉及调节蛋白与一般蛋白质之间的相互作用 转录机械是控制许多生物学的关键机制 过程。基因表达的协调对于健康发展至关重要， 分化，免疫反应和细胞稳态的维持。 在许多人中观察到转录调节计划中的破坏 患病状态，例如癌症。因此，建立一个 了解基本的转录机制。 这项研究的长期目标是了解真核基础 转录因子在转录和基因调节中起作用。模型 主要研究者使用的系统是人类小的转录 核（SN）RNA基因。 SnRNA基因家族代表着大量 在细胞中具有重要功能的基因。这些基因具有相似的 启动子体系结构和RNA聚合酶II转录其中一些 RNA聚合酶III的基因转录了其他基因。因此，这些基因提供了 强大的系统分析两者的转录分子机制 RNA聚合酶II和III。人类snRNA基因的转录 聚合酶特异性，需要基础转录因子称为 SnRNA激活蛋白质复合物（SNAPC）。这种多蛋白质复合物结合 专门针对人SnRNA基因的核心促进剂区域。 Snapc是 由至少五个蛋白质SNAP 19，SNAP43，SNAP45，SNAP5O和SNAP组成 190。此外，TATA-box结合蛋白（TBP）与SNAPC共纯化。 这些蛋白质中的每一个都是由两个RNA进行SnRNA转录所必需的 聚合酶II和III。这些蛋白质也有助于调节 人SnRNA基因的转录。 RNA的人类U6基因转录 聚合酶III被视网膜细胞瘤肿瘤抑制蛋白（RB）抑制 这可能涉及RB和SNAPC之间的沟通。校长 研究人员选择研究SNAPC，因为该复合物在 RNA聚合酶II和III的人SnRNA基因转录是一个 调节蛋白（例如RB）的直接靶标。这个项目将采用 了解SNAPC个体成员的功能的分子技术 用于通过RNA聚合酶II和III的调节转录。