An allelic series of miR-17~92 mutant mice uncovers functional specialization and cooperation among members of a miRNA polycistron

Polycistronic microRNA clusters are a common feature of vertebrate genomes. The coordinated expression of miRNAs belonging to different seed families from a single transcription unit suggests functional cooperation, but this hypothesis has not been experimentally tested. Here we report the characterization of an allelic series of genetically engineered mice harboring selective targeted deletions of individual components of miR-17~92. Our results demonstrate the co-existence of functional cooperation and specialization among members of this cluster, identify a novel function for the miR-17 seed family in controlling axial patterning in vertebrates, and show that loss of miR-19 selectively impairs Myc-driven tumorigenesis in two models of human cancer. By integrating phenotypic analysis and gene expression profiling, we provide a genome-wide view of how components of a polycistronic miRNA-cluster affect gene expression in vivo. The reagents and datasets reported here will accelerate exploration of the complex biological functions of this important miRNA cluster.