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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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要过去十年的研究揭示了长链非编码 RNA (lncRNA) 在控制中的重要性心脏重塑和心力衰竭。我们已经表征了心脏特异性 lncRNA 的控制人和小鼠心肌细胞中的钙处理。敲除该 lncRNA 会导致心肌细胞中的钙处理并损害心脏功能。基因敲除小鼠易患心脏病儿茶酚胺能挑战引起的心律失常和过早死亡。在这个项目中，我们建议（1）确定 lncRNA 在转录水平调节基因表达的机制，(2) 确定 lncRNA如何在选择性剪接水平上调节基因表达，以及（3）确定心脏保护作用由 lncRNA 赋予以响应病理应激。该项目的结果有可能促进心脏病新疗法的开发。