RNA-binding protein RBM24 is required for sarcomere assembly and heart contractility

KL Poon, KT Tan, YY Wei, CP Ng… - Cardiovascular …, 2012 - academic.oup.com
KL Poon, KT Tan, YY Wei, CP Ng, A Colman, V Korzh, XQ Xu
Cardiovascular research, 2012academic.oup.com
Aims 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. 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 …
Aims
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.
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 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.
Conclusion
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.
Oxford University Press