Determinating the role of miRNA in myogenic progenitor maintenance and differentiation

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This application is to support my research program on the cellular mechanisms controlling differentiation of muscle progenitor cells. Many embryonic developmental events, including maintenance of stem and progenitor cells, are regulated post-transcriptionally through expression of small non-translated RNA molecules, called miRNAs. However, we know very little about how miRNA contribute to the maintenance and differentiation of individual tissues. My lab has characterized Ars2, and we and others have shown that it is essential for miRNA biogenesis. Using an in vitro C2C12 cell culture model of differentiation, my lab has shown that Ars2 is necessary for the silencing of self renewal in myogenic progenitor cells, and that myogenic cells deficient for Ars2 are deficient in mature miRNA. In addition, we have identified potential regulator of Ars2 function, called RNPS1, which sequesters Ars2 in the cytoplasm of myoblasts until initiation of differentiation.