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

项目总结/摘要 过去十年的研究已经揭示了长链非编码RNA（lncRNA）在控制细胞凋亡中的重要性。 心脏重塑和心力衰竭我们已经描述了一种心脏特异性lncRNA， 人和小鼠心肌细胞中的钙处理。敲除这种lncRNA会导致 心肌细胞中的钙处理并损害心脏功能。基因敲除小鼠对心脏 引起的心律失常和过早死亡。在本项目中，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如何在可变剪接水平调节基因表达，以及（3）确定心脏保护 是由lncRNA对病理性应激的反应而产生的。该项目的成果有可能 促进心脏病新疗法的发展。

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.