FUNCTION AND REGULATION OF THE HUMAN SPLICING FACTOR SC35

描述（由申请人提供）：作为对no - od -09-058的回应，我们要求对我们现有的GM拨款（5RO1 GM049369-16）进行竞争性补充。标题为“Human Splicing Factor SC35的功能和调控”的亲本基金旨在研究SR蛋白在受调控的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确定心脏中一般和组织特异性剪接调节因子的功能需求通过SR蛋白与其他剪接调控因子的协同作用研究受调控剪接的机制。本亲本基金资助期限为7/01/07至6/30/2011。因此，我们还有两年的时间。在此，我们建议通过竞争性修订机制对该项目进行扩展。亲本补助金是我独立以来的第一个长期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。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，最近在该领域的发现表明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，我们现在提议扩大我们目前的项目，研究SR蛋白与基因组的相互作用，在哺乳动物细胞中转录和RNA加工之间的功能整合。这一扩大的研究项目具有明显的潜力，可以显著提高我们对SR蛋白在发育和疾病中的机制理解。

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.