Authors:
J-F Chen, EP Murchison, R Tang, TE Callis, M Tatsuguchi, Z Deng, M Rojas, SM Hammond, MD Schneider, CH Selzman, G Meissner, C Patterson, GJ Hannon, D-Z Wang
Journal name: 
Proc Natl Acad Sci U S A
Citation info: 
105(6):2111-2116
Abstract: 
Cardiovascular disease is the leading cause of human morbidity and mortality. Dilated cardiomyopathy (DCM) is the most common form of cardiomyopathy associated with heart failure. Here, we report that cardiac-specific knockout of Dicer, a gene encoding a RNase III endonuclease essential for microRNA (miRNA) processing, leads to rapidly progressive DCM, heart failure, and postnatal lethality. Dicer mutant mice show misexpression of cardiac contractile proteins and profound sarcomere disarray. Functional analyses indicate significantly reduced heart rates and decreased fractional shortening of Dicer mutant hearts. Consistent with the role of Dicer in animal hearts, Dicer expression was decreased in end-stage human DCM and failing hearts and, most importantly, a significant increase of Dicer expression was observed in those hearts after left ventricle assist devices were inserted to improve cardiac function. Together, our studies demonstrate essential roles for Dicer in cardiac contraction and indicate that miRNAs play critical roles in normal cardiac function and under pathological conditions.
DOI: 
http://doi.org/10.1073/pnas.0710228105
Research group: 
Hannon Group
E-pub date: 
12 Feb 2008