miR-186 inhibits muscle cell differentiation through myogenin regulation [RNA]

January 2nd, 2014 by Antoniou, A., Mastroyiannopoulos, N. P., Uney, J. B., Phylactou, L. A.

The complex process of muscle differentiation is organized by the myogenic regulatory factors (MRFs), Myf5, MyoD, Myf6 and myogenin, where myogenin plays a critical role in the regulation of the final stage of muscle differentiation. In an effort to investigate the role microRNAs (miRNAs) play in regulating myogenin, a bioinformatics approach was used and six miRNAs (miR-182, miR-186, miR-135, miR-491, miR-329 and miR-96) were predicted to bind the myogenin 3 untranslated region (UTR). However, luciferase assays showed only miR-186 inhibited translation and 3 UTR mutagenesis analysis confirmed this interaction was specific. Interestingly, the expression of miR-186 mirrored that of its host gene, ZRANB2, during development. Functional studies demonstrated that miR-186 overexpression inhibited the differentiation of C2C12 and primary muscle cells. Our findings therefore identify miR-186 as a novel regulator of myogenic differentiation.