Understanding how multiple micro RNAs (miRNAs) regulate their targets genome-wide holds promise for deciphering complex cellular regulatory networks. In this study, Hoefert et al. use CLEAR-CLIP to dissect miRNA-200 family targeting and reveal a novel role for these miRNAs in regulating cell adhesion and hair follicle morphogenesis.

The microRNA (miRNA) pathway is a widespread mechanism of post-transcriptional gene regulation in eukaryotic cells. In animals, each miRNA species can regulate hundreds of protein coding genes, resulting in pervasive functions for miRNAs in numerous cellular processes. Since the identification of the first mammalian miRNA, the function of miRNAs in mammals has been a topic of great interest, both because of the versatile roles of miRNAs in biological systems, as well as the clinical potential of these regulatory RNAs. With well-defined cell lineages and the availability of versatile tools for both in vivo and in vitro studies, mammalian skin has emerged as an important system in which to examine miRNAs’ functions in adult tissues. In this review, we discuss recent insights into the functions and regulatory networks of miRNAs in mammals, with a specific focus on murine skin development as a model system. We first introduce functional analyses of the miRNA biogenesis pathway in the skin, then highlight the functions of individual miRNAs in skin development, followed by an examination of miRNA roles in skin stress responses. We finish with a discussion of miRNA regulatory networks and emphasize future challenges and emerging technologies that permit the genome-wide study of miRNA functions and regulatory mechanisms in mammalian skin.