PRE-MRNA SPLICE SITE RECOGNITION IN HUMAN DISEASE

人类疾病中的前 mRNA 剪接位点识别

• 批准号: 8170273
• 负责人: CLARA KIELKOPF
• 金额: $ 0.1万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170273
• 关键词: Binding; Complex; Computer Retrieval of Information on Scientific Projects Database; Disease; Foundations; Funding; Goals; Grant; Inherited; Institution; Light; Phosphorylation; RNA Splicing; Research; Research Personnel; Resources; Signal Transduction; Site; Source; Staging; Structure; United States National Institutes of Health; Work; human disease; mRNA Precursor; novel; three dimensional structure

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall goal of our research is to understand the three-dimensional structures that guide pre-mRNA splicing, and to thereby provide a foundation to develop treatments for inherited diseases associated with errors in splice site recognition. During the critical early stages of splice site choice, the essential splicing factor U2AF cooperatively recognizes the pre-mRNA splice site as a complex with Splicing Factor 1 (SF1). This interaction is regulated by phosphorylation of key SF1 domain that contributes to U2AF binding, but lacks detectable homology with known structures. The primary aim of the proposed work is to determine the crystal structure of this key SF1 domain. The novel structure of this SF1 domain would shed light on the means of action by this important splicing factor. In addition, we recently obtained crystals of the phosphorylated state of the SF1 domain, which would reveal signal-dependent conformational changes.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们研究的总体目标是了解指导前mRNA剪接的三维结构，从而为开发与剪接位点识别错误相关的遗传病的治疗提供基础。在剪接位点选择的关键早期阶段，基本剪接因子U2AF协同识别前mRNA剪接位点为与剪接因子1(SF1)的复合体。这种相互作用受关键的SF1结构域的磷酸化调节，该结构域有助于U2AF结合，但缺乏与已知结构的可检测到的同源性。拟议工作的主要目的是确定该关键SF1结构域的晶体结构。这种SF1结构域的新颖结构将有助于阐明这一重要剪接因子的作用方式。此外，我们最近获得了SF1结构域的磷酸化状态的晶体，这将揭示信号依赖的构象变化。