Institute of Molecular and Cell Biology, 61 Biopolis Dr., #08-13 Proteos, Singapore 138673, Singapore.
Cardiovasc Res. 2012 Jun 1;94(3):418-27. doi: 10.1093/cvr/cvs095. Epub 2012 Feb 15.
The factors responsible for cardiomyopathy are not fully understood. Our studies of the transcriptome of human embryonic stem cell-derived cardiomyocytes identified novel genes up-regulated during cardiac differentiation, including RBM24. We therefore studied how its deficiency affected heart development.
The expression of Rbm24 was detected in mouse cardiomyocytes and embryonic myocardium of zebrafish at the RNA and protein level. The Rbm24 loss-of-function showed that Rbm24 deficiency resulted in a reduction in sarcomeric proteins, Z-disc abnormality, and diminished heart contractility, resulting in the absence of circulation in zebrafish embryos. Gene expression profiling revealed down-regulation of multiple pathways associated with sarcomere assembly and vasculature development in Rbm24 deficiency.
We identified a novel role of the tissue-specific RNA-binding protein (RBP) Rbm24 involving in the regulation of cardiac gene expression, sarcomeric assembly, and cardiac contractility. This study uncovers a potential novel pathway to cardiomyopathy through down-regulation of the RBP Rbm24.
导致心肌病的因素尚未完全阐明。我们对人胚胎干细胞衍生的心肌细胞转录组的研究确定了在心脏分化过程中上调的新基因，包括 RBM24。因此，我们研究了其缺乏如何影响心脏发育。
在 RNA 和蛋白质水平检测了 Rbm24 在小鼠心肌细胞和斑马鱼胚胎心肌中的表达。Rbm24 功能丧失显示，Rbm24 缺乏导致肌节蛋白减少、Z 盘异常和心脏收缩力减弱，导致斑马鱼胚胎循环缺失。基因表达谱分析显示，Rbm24 缺乏时与肌节组装和血管发育相关的多个途径下调。
我们确定了组织特异性 RNA 结合蛋白 (RBP) Rbm24 的一个新作用，该作用涉及心脏基因表达、肌节组装和心脏收缩力的调节。这项研究通过下调 RBP Rbm24 揭示了一种潜在的导致心肌病的新途径。
