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


Authors: 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.
Article Title: An allelic series of miR-171/492-mutant mice uncovers functional specialization and cooperation among members of a microRNA polycistron
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. © 2015 Nature America, Inc. All rights reserved.
Keywords: unclassified drug; nonhuman; mouse; phenotype; allele; homologous recombination; mus; microrna; gene expression; gene expression profiling; in vivo study; carcinogenesis; vertebrata; specialization; sequence homology; vertebrate; heart development; rna sequence; biological functions; reverse transcription; microrna 17 92; lung hypoplasia; priority journal; article
Journal Title: Nature Genetics
Volume: 47
Issue: 7
ISSN: 1061-4036
Publisher: Nature Publishing Group  
Date Published: 2015-07-01
Start Page: 766
End Page: 775
Language: English
DOI: 10.1038/ng.3321
PROVIDER: scopus
PMCID: PMC4485521
PUBMED: 26029871
DOI/URL:
Notes: Export Date: 3 August 2015 -- Source: Scopus
Altmetric Score