Kar Lai POON1, Kar Tong TAN2, Yang Ye WEI3, Chee Peng NG1, Alan COLMAN2, Vladimir KORZH1,4, Xiu Qin XU2,3
1 - Institute of Molecular and Cell Biology, Singapore
2 - Singapore Stem Cell Consortium, Institute of Medical Biology Singapore
3 - Institute of Stem Cell and Regenerative Medicine, Medical College, Xiamen University, China
4 - Department of Biological Sciences, National University of Singapore, Singapore
Published online in Cardiovascular Res, on February 15, 2012
The factors responsible for cardiomyopathy are not fully understood. Our studies of the transcriptome of human embryonic stem cells (hESC)-derived cardiomyocytes identified novel genes up-regulated during cardiac differentiation including RBM24. We therefore studied how its deficiency affected heart development.
. We therefore studied how its deficiency affected heart development.
Methods and Results: 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 of sarcomeric proteins, Z discs abnormality and diminished heart contractility resulting in 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.
Conclusions: We identified a novel role of the tissue-specific RNA binding protein Rbm24, involving regulation of cardiac gene expression, sarcomeric assembly and cardiac contractility. This study uncovers a potentially novel pathway to cardiomyopathy through down-regulation of the RNA-binding protein Rbm24.
A deficiency of the novel RNA-binding protein RBM24 (discovered in human stem cells) in embryonic zebrafish caused a reduction in the number of trabeculae and hypertrophy of those that remain. These myofibrillary structures of the heart ventricle ensure an efficient heart constriction and blood circulation. Their anomaly mimics cardiomyopathy, one of the pathological conditions taking place in humans and links Rbm24 with this disease.
For more information on Vladimir KORZH's lab, please click here.