Alternative mRNA processing in cardiac hypertrophy

心脏肥大中的替代 mRNA 加工

基本信息

批准号：
7773652
负责人：
BIN TIAN
金额：
$ 19.5万
依托单位：
UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-01-01 至 2011-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7773652
关键词：
Alternative Splicing Biological Assay Cardiac Cardiac Myocytes Cardiomegaly Cause of Death Computing Methodologies Data Development Disease Elements Event Exons Extracellular Structure Fetus Foundations Future Gene Expression Gene Expression Profile Gene Expression Regulation Genes Genetic Transcription Goals Growth Heart Heart Diseases Heart Hypertrophy Heart failure Human Hypertrophy Knowledge Lead Left ventricular structure Light Mammalian Cell Mechanics Messenger RNA MicroRNAs Molecular Mus Pattern Physiology Play Polyadenylation Process RNA Splicing RNA-Binding Proteins Regulation Regulatory Element Reporter Reporting Reverse Transcription Role Signal Pathway Site Solid Staging Techniques Therapeutic United States cardiogenesis constriction design effective therapy fetal genome-wide pressure programs public health relevance response

项目摘要

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.

描述（由申请人提供）：替代mRNA加工事件，例如替代剪接（AS）和替代聚腺苷酸化（APA），有助于哺乳动物细胞中转录组的复杂性，并在心脏的发育和疾病中起重要作用。心脏肥大是对增加的机械负荷响应的心脏增大，这涉及心肌大小的生长以及心脏生理方面的重塑。在肥大期间，调节了几种信号通路，导致许多基因转录的变化。最近的报道也暗示了肥大期间转录后基因调控中的microRNA。我们的长期目标是了解心脏肥大中的转录和转录后基因表达机制。我们针对该项目有3个具体目标：1）检查心脏肥大中的替代mRNA加工事件； 2）比较心脏肥大中的替代mRNA加工曲线与早期发育中的曲线； 3）阐明心脏肥大中替代mRNA加工的机制。该探索性/发展项目将使用计算分析和实验测定法系统地检查心脏肥大中的替代mRNA加工。结果将显着丰富我们对心脏肥大中转录后基因调控的了解，并阐明潜在的心力衰竭治疗疗法。公共卫生相关性：心脏肥大是由于机械负荷增加而导致心力衰竭的心脏增大。心力衰竭是美国死亡的主要原因之一。了解心脏肥大的分子机制将有助于我们设计有效的疗法来减轻或治愈疾病。