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

项目摘要/摘要 过去十年的研究揭示了长非编码RNA(LncRNAs)在控制中的重要性 心脏重塑和心力衰竭。我们已经确定了心脏特异的lncRNA在控制 人和小鼠心肌细胞的钙处理。这种lncRNA的敲除导致了 心肌细胞中的钙处理会损害心脏功能。基因敲除小鼠易患心脏病 儿茶酚胺能刺激和过早死亡引起的心律失常。在这个项目中，我们建议(1) 确定lncRNA在转录水平上调节基因表达的机制，(2)确定 LncRNA如何在选择性剪接水平调节基因表达，以及(3)决定心脏保护 由lncRNA对病理性压力做出的反应。这个项目的结果有可能 促进心脏病新疗法的开发。

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.