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Nat. Genet., Published online 01 June 2015 | doi:10.1038/ng.3321
An allelic series of miR-17~92–mutant mice uncovers functional specialization and cooperation among members of a microRNA polycistron
Abstract
Yoon-Chi Han1,2,10, Joana A Vidigal1,10, Ping Mu1,3,10, Evelyn Yao1,3, Irtisha Singh4, Alvaro J Gonzalez4, Carla P Concepcion1,3, Ciro Bonetti1, Paul Ogrodowski1, Brett Carver5,6, Licia Selleri7, Doron Betel8,9, Christina Leslie4 & Andrea Ventura1
1Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA. 2Oncology Research Unit, Pfizer, Inc., Pearl River, New York, USA. 3Weill Cornell Graduate School of Medical Sciences of Cornell University, New York, New York, USA. 4Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA. 5Human Oncology and Pathogenesis Program. Memorial Sloan Kettering Cancer Center, New York, New York, USA. 6Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA. 7Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, New York, USA. 8Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medical College, New York, New York, USA. 9Institute for Computational Biomedicine, Weill Cornell Medical College, New York, New York, USA. 10These authors contributed equally to this work.
Correspondence to : Andrea Ventura
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-17~92 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
논문정보
- Research article
- 2015년 06월 (BRIC 등록일 2015-06-04)
- 국외 연구진
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