An allelic series of miR-171/492-mutant mice uncovers functional specialization and cooperation among members of a microRNA polycistron

Yoon Chi Han, Joana A. Vidigal, Ping Mu, Evelyn Yao, Irtisha Singh, Alvaro J. González, Carla P. Concepcion, Ciro Bonetti, Paul Ogrodowski, Brett Carver, Licia Selleri, Doron Betel, Christina Leslie, Andrea Ventura

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

Polycistronic microRNA (miRNA) clusters are a common feature of vertebrate genomes. The coordinated expression of miRNAs belonging to different seed families from a single transcriptional 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 the miR-171/492 cluster. Our results demonstrate the coexistence of functional cooperation and specialization among members of this cluster, identify a previously undescribed 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 the components of a polycistronic miRNA cluster affect gene expression in vivo. The reagents and data sets reported here will accelerate exploration of the complex biological functions of this important miRNA cluster.

Original languageEnglish (US)
Pages (from-to)766-775
Number of pages10
JournalNature genetics
Volume47
Issue number7
DOIs
StatePublished - Jun 26 2015
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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    Han, Y. C., Vidigal, J. A., Mu, P., Yao, E., Singh, I., González, A. J., Concepcion, C. P., Bonetti, C., Ogrodowski, P., Carver, B., Selleri, L., Betel, D., Leslie, C., & Ventura, A. (2015). An allelic series of miR-171/492-mutant mice uncovers functional specialization and cooperation among members of a microRNA polycistron. Nature genetics, 47(7), 766-775. https://doi.org/10.1038/ng.3321