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Specific requirements of MRFs for the expression of muscle specific microRNAs, miR-1, miR-206 and miR-133

2008; Elsevier BV; Volume: 321; Issue: 2 Linguagem: Inglês

10.1016/j.ydbio.2008.06.019

1095-564X

Dylan Sweetman, Katarzyna Goljanek, Tina Rathjen, Svetlana Oustanina, Thomas Braun, Tamás Dalmay, Andrea Münsterberg,

RNA Research and Splicing

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.