MyoD and Twist-1 are transcription factors that are known to, respectively, promote and inhibit muscle cell differentiation. MyoD can affect myogenesis by regulating the expression of muscle-specific micro (mi)RNAs, and Twist-1 expression in cancer has been shown to be modulated by miRNAs; but the underlying details are unclear. In their work on page , Leonidas Phylactou and colleagues used human myoblast cells to uncover a so-far-unknown regulatory mechanism that involves MyoD, miR-206 and Twist-1. By using prediction software and a luciferase reporter, the authors identified a functional miR-206 response element in the 3’UTR of human Twist-1 mRNA. Overexpression of miR-206 resulted in decreased levels of Twist-1 and increased differentiation of muscle cells, whereas the opposite effects on Twist-1 and differentiation were observed when miR-206 was inhibited, thus demonstrating that Twist-1 is a target of miR-206 and that its levels affect myogenesis. The authors then went on to show that MyoD bound to the miR-206 promoter and that, consequently, overexpression of MyoD led to increased levels of miR-206 and decreased levels of Twist-1, which – in turn – increased differentiation. Finally, they succeeded in significantly improving myogenesis in cells from patients that suffer from congenital myotonic dystrophy type-1 (DM1), by either overexpressing MyoD or transfecting them with miR-206. In conclusion, this study describes a new mechanism that involves MyoD-mediated induction of miR206 and its subsequent inhibition of Twist-1, and that could be exploited for the therapy of diseases that are associated with defects in myogenesis.
