Specific requirements of MRFs for the expression of muscle specific microRNAs, miR-1, miR-206 and miR-133.
The expression of three microRNAs, miR-1, miR-206 and miR-133 is restricted to skeletal myoblasts and cardiac tissue during embryo development and muscle cell differentiation, which suggests a regulation by muscle regulatory factors (MRFs). Here we show that inhibition of C2C12 muscle cell differentiation by FGFs, which interferes with the activity of MRFs, suppressed the expression of miR-1, miR-206 and miR-133. To further investigate the role of myogenic regulators (MRFs), Myf5, MyoD, Myogenin and MRF4 in the regulation of muscle specific microRNAs we performed gain and loss-of-function experiments in vivo, in chicken and mouse embryos. We found that directed expression of MRFs in the neural tube of chicken embryos induced ectopic expression of miR-1 and miR-206. Conversely, the lack of Myf5 but not of MyoD resulted in a loss of miR-1 and miR-206 expression. Taken together our results demonstrate differential requirements of distinct MRFs for the induction of microRNA gene expression during skeletal myogenesis.
Sweetman
Dylan
D
School of Biological Sciences, University of East Anglia, Norwich, Norfolk, NR4 7TJ, UK. d.sweetman@uea.ac.uk
Goljanek
Katarzyna
K
Rathjen
Tina
T
Oustanina
Svetlana
S
Braun
Thomas
T
Dalmay
Tamas
T
Münsterberg
Andrea
A
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002642:Chick Embryo; D005346:Fibroblast Growth Factors / Q000378:metabolism; D017403:In Situ Hybridization; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D008969:Molecular Sequence Data; D024510:Muscle Development / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism*; D018006:Myogenic Regulatory Factors / Q000378:metabolism*; D054259:Neural Tube / Q000378:metabolism*; D016415:Sequence Alignment
D035683:MicroRNAs; D018006:Myogenic Regulatory Factors; D005346:Fibroblast Growth Factors