MOLECULAR ANALYSIS OF BASAL TRANSCRIPTION FACTOR SNAPC

描述(改编自申请人的摘要)：转录规则 涉及调控蛋白和一般蛋白之间的相互作用 转录机制，是控制许多生物的关键机制 流程。基因表达的协调对健康发展至关重要， 分化、免疫反应和维持细胞内环境平衡。 在转录调控程序中观察到许多中断 疾病状态，如癌症。因此，开发一种 对基本转录机制的理解。 这项研究的长期目标是了解真核生物是如何 转录因子在转录和基因调控中发挥作用。模型 首席研究员使用的系统是人类小分子的转录 核(Sn)RNA基因。SnRNA基因家族代表了一大批 在细胞中具有重要功能的基因。这些基因有相似的 启动子的结构和RNA聚合酶II转录其中的一些 而RNA聚合酶III转录其他基因。因此，这些基因提供了一种 分析两者转录分子机制的强大系统 RNA聚合酶II和III.人类SnRNA基因的转录，与 聚合酶的专一性，需要基础转录因子称为 SnRNA激活蛋白复合体(SNAPc)。这种多蛋白复合体结合 具体到人类SnRNA基因的核心-启动子区域。SNAPc为 由至少5种蛋白质SNAP 19、SNAP43、SNAP45、SNAP50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由两个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 人类单链RNA基因的转录。人U6基因的RNA转录 视网膜母细胞瘤肿瘤抑制蛋白(Rb)抑制聚合酶III 这可能涉及RB和SNAPC之间的通信。校长 研究人员选择研究SNAPc，因为这个复合体在 人SnRNA基因由RNA聚合酶II和III转录，是一种 Rb等调控蛋白的直接靶标。该项目将雇用 了解SNAPc单个成员功能的分子技术 用于RNA聚合酶II和III的转录调控。

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.