MOLECULAR ANALYSIS OF BASAL TRANSCRIPTION FACTOR SNAPC

基础转录因子 SNAPC 的分子分析

• 批准号: 6636338
• 负责人: Ronald William HENRY
• 金额: $ 19.26万
• 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/6636338
• 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（改编自申请人摘要）：转录调控 包括调节蛋白和一般的 转录机制，是控制许多生物学过程的关键机制。 流程.基因表达的协调对健康发育至关重要， 分化、免疫应答和维持细胞内稳态。 在许多细胞中观察到转录调控程序的中断， 疾病状态，如癌症。因此，重要的是要制定一个 理解基本的转录机制。 这项研究的长期目标是了解真核生物的基础 转录因子在转录和基因调控中起作用。模型 主要研究者使用的系统是人类小细胞的转录， 核（sn）RNA基因。snRNA基因家族代表了一个大的集合， 在细胞中有重要功能的基因。这些基因具有相似的 启动子结构，但RNA聚合酶II转录其中一些 而RNA聚合酶III转录其他基因。因此，这些基因提供了 强大的系统来分析转录的分子机制， RNA聚合酶II和III。人类snRNA基因的转录，无论 聚合酶特异性，需要基础转录因子，称为 snRNA激活蛋白复合物（SNAPc）。这种多蛋白质复合物 特异性针对人snRNA基因的核心启动子区。SNAPc是 由至少五种蛋白质SNAP 19、SNAP 43、SNAP 45、SNAP 50和SNAP组成 190.此外，TATA盒结合蛋白（TBP）与SNAPc共纯化。 这些蛋白质中的每一种都是两种RNA转录snRNA所必需的。 聚合酶II和III。这些蛋白质也有助于调节 人类snRNA基因的转录。人U6基因转录（RNA） 聚合酶III被视网膜母细胞瘤肿瘤抑制蛋白（Rb）抑制 这可能涉及Rb和SNAPc之间的通信。校长 研究人员选择研究SNAPc，因为这种复合物在 人snRNA基因通过RNA聚合酶II和III转录，是一种 调节蛋白如Rb的直接靶点。该项目将采用 了解SNAPc单个成员功能的分子技术 用于RNA聚合酶II和III的调节转录。