FUNCTION AND REGULATION OF THE HUMAN SPLICING FACTOR SC35

描述（由申请人提供）：我们要求对我们现有的通用汽车赠款（5 RO 1 GM 049369 -16）进行竞争性补充，以回应NOT-OD-09-058。标题为“人类剪接因子SC 35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子的功能要求3.利用SR蛋白与其他剪接调控因子的协同作用研究剪接调控机制本基金的资助期为2007年7月1日至2011年6月30日。这样，我们还有两年时间。在这里，我们建议通过竞争性修订机制扩展该项目。父母资助是我成为独立以来第一个也是持久的RO 1，它一直支持我们努力解码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一个转折，揭示了SR蛋白在转录延伸中具有直接作用，并且该领域最近的一项发现表明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。这个扩大的研究计划有明显的潜力，以显着提高我们的SR蛋白在发育和疾病的机制的理解。 公共卫生相关性：该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。

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.