| Cdk9 is the catalytic core of the positive transcription elongation factor b (P-TEFb) and regulates transcriptional elongation factors by
phosphorylation of RNA pol II. Apart from its role on myogenic gene expression, Cdk9 regulation of muscle-specific microRNAs in the early
stage of cardiomyogenesis is poorly understood. Here we demonstrate that Cdk9 not only regulates myogenic transcription factors, but also
controls muscle-specific microRNAs. During cardiac differentiation of mouse embryonic stem cells, high Cdk9 expression preceded
up-regulation of miR-1. To investigate potential regulatory roles of Cdk9 on cardiac microRNAs and myogenesis genes, we overexpressed
Cdk9 in myoblast C2C12 cells, which resulted in significant induction of miR-1 and miR-206, while miR-133 was downregulated. Moreover,
expression levels of MyoD and Srf, key regulators of myogenesis, also increased in cells with overexpression of Cdk9. We further observed
Cdk9-mediated apoptosis in C2C12 cells corresponding to induction of miR-1 expression levels. Thus, Cdk9 plays a complex role in myocyte
progenitor differentiation and apoptosis by regulating myogenic protein and muscle-specific microRNA expression. |