Alternative mRNA processing in cardiac hypertrophy

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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.