Alternative mRNA processing in cardiac hypertrophy

描述（由申请人提供）：备选mRNA加工事件，如备选剪接（as）和备选聚腺苷酸化（APA），增加了哺乳动物细胞转录组的复杂性，并在心脏发育和疾病中发挥重要作用。心脏肥大是由于机械负荷增加而引起的心脏增大，包括心肌细胞大小的增加和心脏生理各方面的重塑。在肥大过程中，一些信号通路受到调节，导致许多基因的转录发生变化。最近的报道也暗示了在肥大过程中microrna参与转录后基因调控。我们的长期目标是了解心肌肥大的转录和转录后基因表达机制。我们对这个项目有3个具体目标：1)研究心肌肥厚中不同的mRNA加工事件；2)比较心肌肥厚与早期心肌肥厚的mRNA加工谱；3)阐明心肌肥厚中选择性mRNA加工的机制。这个探索性/发展性项目将通过计算分析和实验分析系统地研究心肌肥厚中不同的mRNA加工过程。该结果将显著丰富我们对心肌肥厚转录后基因调控的认识，并揭示心力衰竭的潜在治疗方法。

DESCRIPTION (provided by applicant): Alternative mRNA processing events, such as alternative splicing (AS) and alternative polyadenylation (APA), contribute to the complexity of transcriptome in mammalian cells, and play significant roles in development and disease of the heart. Cardiac hypertrophy is enlargement of heart in response to increased mechanical load, which involves growth of cardiac myocytes in size, and remodeling of aspects of cardiac physiology. Several signaling pathways are regulated during hypertrophy, leading to change of transcription for many genes. Recent reports also implicated microRNAs in post-transcriptional gene regulation during hypertrophy. Our long term goal is to understand transcriptional and post-transcriptional gene expression mechanisms in cardiac hypertrophy. We have 3 specific aims for this project: 1) To examine alternative mRNA processing events in cardiac hypertrophy; 2) To compare the alternative mRNA processing profiles in cardiac hypertrophy with those in early development; 3) To elucidate the mechanisms of alternative mRNA processing in cardiac hypertrophy. This exploratory/developmental project will systematically examine alternative mRNA processing in cardiac hypertrophy using computational analyses and experimental assays. The results will significantly enrich our knowledge about post-transcriptional gene regulation in cardiac hypertrophy, and shed light on potential therapeutics for heart failure. PUBLIC HEALTH RELEVANCE: Cardiac hypertrophy is enlargement of the heart in response to increased mechanical load, which often leads to heart failure. Heart failure is one of the leading causes of death in the United States. Understanding the molecular mechanism underlying cardiac hypertrophy will help us design effective therapies to mitigate or cure the disease.