Several genes have been associated with dilated cardiomyopathy (DCM), a condition conferring risk of heart failure and sudden death. Among these is RNA-binding motif protein 20 (RBM20), with mutations present in ∼3% of individuals with DCM. Guo et al. now characterise a spontaneous rat model that explains how defects in RBM20 function can cause cardiomyopathy and provides insight into normal regulation of heart function. The mutant rats were known to have impaired splicing of titin, a sarcomeric protein that confers structure and function to striated muscle. Guo et al. determined that RBM20 is required for titin splicing, as well as for alternative splicing of many other conserved cardiac genes, as revealed by deep sequencing of rat and human samples. Defective splicing caused by Rbm20 mutation in rats results in features resembling those of humans carrying RBM20 mutations, including left ventricular dilatation, subendocardial fibrosis, arrhythmia and sudden death. These data explain how RBM20 mutations cause disease in a subset of individuals with DCM, and identify RBM20 as a global regulator of heart function by controlling the alternative splicing of specific cardiac genes.

Guo W., Schafer S., Greaser M. L., Radke M. H., Liss M., Govindarajan T., Maatz H., Schulz H., Li S., Parrish A. M., et al. (2012). RBM20, a gene for hereditary cardiomyopathy, regulates titin splicing. Nat. Med. [Epub ahead of print] doi: https://doi.org/10.1038/nm.2693.
Google Scholar
 

Written by editorial staff. © 2012. Published by The Company of Biologists Ltd
2012
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Share Alike License (http://creativecommons.org/licenses/by-nc-sa/3.0), which permits unrestricted non-commercial use, distribution and reproduction in any medium provided that the original work is properly cited and all further distributions of the work or adaptation are subject to the same Creative Commons License terms