Essential role for Dicer during skeletal muscle development.
microRNAs (miRNAs) regulate gene expression post-transcriptionally by targeting mRNAs for degradation or by inhibiting translation. Dicer is an RNase III endonuclease which processes miRNA precursors into functional 21-23 nucleotide RNAs that are subsequently incorporated into the RNA-induced silencing complex. miRNA-mediated gene regulation is important for organogenesis of a variety of tissues including limb, lung and skin. To gain insight into the roles of Dicer and miRNAs in mammalian skeletal muscle development, we eliminated Dicer activity specifically in the myogenic compartment during embryogenesis. Dicer activity is essential for normal muscle development during embryogenesis and Dicer muscle mutants have reduced muscle miRNAs, die perinatally and display decreased skeletal muscle mass accompanied by abnormal myofiber morphology. Dicer mutant muscles also show increased apoptosis and Cre-mediated loss of Dicer in Myod-converted myoblasts results in enhanced cell death. These observations demonstrate key roles for Dicer in skeletal muscle and implicate miRNAs as critical components required for embryonic myogenesis.
O'Rourke
Jason R
JR
Department of Molecular Genetics and Microbiology and the Genetics Institute, University of Florida, College of Medicine, Gainesville, FL 32610-0266, USA.
Georges
Sara A
SA
Seay
Howard R
HR
Tapscott
Stephen J
SJ
McManus
Michael T
MT
Goldhamer
David J
DJ
Swanson
Maurice S
MS
Harfe
Brian D
BD
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002470:Cell Survival; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009024:Morphogenesis; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology* / Q000201:enzymology* / Q000473:pathology; D009210:Myofibrils / Q000473:pathology / Q000502:physiology; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism*
D035683:MicroRNAs; D043244:Ribonuclease III