FUNCTION AND REGULATION OF THE HUMAN SPLICING FACTOR SC35

人类剪接因子 SC35 的功能和调控

• 批准号: 7845881
• 负责人: XIANG-DONG FU
• 金额: $ 31.01万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7845881
• 关键词: Development; Disease; Family; Funding; Genetic Transcription; Genome; Grant; Heart; Histones; Mammalian Cell; Methods; Proteins; RNA Binding; RNA Processing; RNA Splicing; Regulation; Research; Research Design; Role; Site; Tail; Tissue-Specific Splicing; base; cardiogenesis; design; human SFRS2 protein; parent grant; programs; public health relevance; response

DESCRIPTION (provided by applicant): We request a competitive supplement to our existing GM grant (5RO1 GM049369-16) in response to NOT-OD-09-058. The parent grant under the title "Function and Regulation of the Human Splicing Factor SC35" was designed to study the role of SR proteins in regulated RNA processing, focusing on the following 3 specific aims: 1. Analyze the splicing program during heart development 2. Determine the functional requirement of general and tissue-specific splicing regulators in the heart 3. Study the mechanism of regulated splicing by the synergy between SR proteins and other splicing regulators The funding period of this parent grant is from 7/01/07 to 6/30/2011. We thus have two years remaining. Here we propose an extension of this project via the competitive revision mechanism. The parent grant is my first and long-lasting RO1 since becoming independent, which has been supporting our efforts in decoding the function of SR proteins as a family of RNA binding splicing factors and regulators. Our recent discovery marked a turn of this project, revealing that SR proteins have a direct role in transcriptional elongation and a recent finding in the field indicates that SR proteins can interact directly with the tail of histone 3. Based on these recent advances, we now propose to expand our current project to study the interaction of SR proteins with the genome for functional integration between transcription and RNA processing in mammalian cells. This expanded research program has a clear potential to significantly enhance our mechanistic understanding of SR proteins in development and disease. PUBLIC HEALTH RELEVANCE: The proposed project is designed to determine the role of SR proteins in defining splice site by interacting with the genome, which has potential to reveal disease mechanisms.

描述（由申请人提供）：我们请求对现有 GM 拨款 (5RO1 GM049369-16) 进行竞争性补充，以响应 NOT-OD-09-058。题为“人类剪接因子 SC35 的功能和调节”的母基金旨在研究 SR 蛋白在调节 RNA 加工中的作用，重点关注以下 3 个具体目标： 1. 分析心脏发育过程中的剪接程序 2. 确定心脏中一般和组织特异性剪接调节因子的功能需求 3. 通过 SR 蛋白与其他剪接之间的协同作用来研究调节剪接的机制 监管机构 本次家长补助金的资助期限为 2011 年 7 月 1 日至 6 月 30 日。因此，我们还剩下两年时间。在这里，我们建议通过竞争性修订机制对该项目进行扩展。家长资助是我独立以来的第一个也是长期的 RO1，它一直支持我们解码 SR 蛋白作为 RNA 结合剪接因子和调节因子家族的功能的努力。我们最近的发现标志着这个项目的转折，揭示了 SR 蛋白在转录延伸中具有直接作用，并且该领域的最新发现表明 SR 蛋白可以直接与组蛋白 3 的尾部相互作用。基于这些最新进展，我们现在建议扩展我们当前的项目，以研究 SR 蛋白与基因组的相互作用，以实现哺乳动物细胞中转录和 RNA 加工之间的功能整合。这项扩展的研究计划具有明显的潜力，可以显着增强我们对发育和疾病中 SR 蛋白的机制理解。 公共健康相关性：拟议项目旨在通过与基因组相互作用来确定 SR 蛋白在定义剪接位点中的作用，这有可能揭示疾病机制。