Regulation of gene transcription and alternative splicing by a long non-coding RNA

长非编码RNA对基因转录和选择性剪接的调控

• 批准号: 10693874
• 负责人: Kunhua Song
• 金额: $ 54.64万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10693874
• 关键词: Address; Agreement; Alternative Splicing; American; Arginine; Arrhythmia; Binding; Biopsy; Ca(2+)-Transporting ATPase; Calcium; Cardiac; Cardiac Myocytes; Catecholaminergic Polymorphic Ventricular Tachycardia; Catecholamines; Cell Nucleus; Cells; Cessation of life; Chromatin; Coupling; Data; Defect; Development; Dihydropyridine Receptors; Down-Regulation; Exercise; Exons; Functional disorder; Gene Expression; Gene Expression Regulation; Genes; Genetic Transcription; Heart; Heart Diseases; Heart failure; Homeostasis; Human; Impairment; Individual; Isoproterenol; Knock-out; Knockout Mice; Mechanics; Membrane; Membrane Potentials; Messenger RNA; Molecular; Mus; Muscle Cells; Mutation; Myocardium; Nuclear; Pathogenesis; Pathologic; Patients; Predisposition; Promoter Regions; Protein Isoforms; RNA Splicing; Regulation; Research; Role; Ryanodine Receptor Calcium Release Channel; Sarcoplasmic Reticulum; Serine; Signal Transduction; Skeletal Muscle; Stress; Transcript; Transcriptional Regulation; Untranslated RNA; chromosome conformation capture; exercise capacity; genome-wide; heart function; mRNA Precursor; novel therapeutics; overexpression; premature; pressure; promoter; recruit; response; sudden cardiac death; therapeutic target; triadin

Project Summary/Abstract Research over the past decade has revealed the importance of long non-coding RNAs (lncRNAs) in the control of cardiac remodeling and heart failure. We have characterized a cardiac specific lncRNA in the control of calcium handling in human and mouse cardiomyocytes. Knockout of this lncRNA causes dysregulation of calcium handling in cardiomyocytes and impairs cardiac function. Knockout mice are susceptible to cardiac arrhythmias caused by catecholaminergic challenging and premature death. In this project, we propose to (1) determine mechanisms by which lncRNA regulates gene expression at the transcription level, (2) determine how lncRNA regulates gene expression at the alternative splicing level, and (3) determine cardiac protection conferred by lncRNA in response to pathological stresses. The results from this project have the potential to facilitate the development of novel therapeutics for heart disease.

项目总结/文摘