Rexiati Maimaiti, Sun Mingming, Guo Wei
Animal Science, University of Wyoming, Laramie, WY 82071, USA.
Center for Cardiovascular Research and integrative medicine, University of Wyoming, Laramie, WY 82071, USA.
Genes (Basel). 2018 Jan 5;9(1):18. doi: 10.3390/genes9010018.
Alternative splicing is an essential post-transcriptional process to generate multiple functional RNAs or proteins from a single transcript. Progress in RNA biology has led to a better understanding of muscle-specific RNA splicing in heart disease. The recent discovery of the muscle-specific splicing factor RNA-binding motif 20 (RBM20) not only provided great insights into the general alternative splicing mechanism but also demonstrated molecular mechanism of how this splicing factor is associated with dilated cardiomyopathy. Here, we review our current knowledge of muscle-specific splicing factors and heart disease, with an emphasis on RBM20 and its targets, RBM20-dependent alternative splicing mechanism, RBM20 disease origin in induced Pluripotent Stem Cells (iPSCs), and RBM20 mutations in dilated cardiomyopathy. In the end, we will discuss the multifunctional role of RBM20 and manipulation of RBM20 as a potential therapeutic target for heart disease.
可变剪接是一种重要的转录后过程，可从单个转录本产生多种功能性RNA或蛋白质。RNA生物学的进展使人们对心脏病中肌肉特异性RNA剪接有了更好的理解。肌肉特异性剪接因子RNA结合基序20（RBM20）的最新发现不仅为一般的可变剪接机制提供了深刻见解，还揭示了该剪接因子与扩张型心肌病相关的分子机制。在此，我们综述了目前关于肌肉特异性剪接因子与心脏病的知识，重点关注RBM20及其靶点、RBM20依赖性可变剪接机制、诱导多能干细胞（iPSC）中RBM20的疾病起源以及扩张型心肌病中的RBM20突变。最后，我们将讨论RBM20的多功能作用以及将RBM20作为心脏病潜在治疗靶点的调控。
