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Norway

PMID:26029871  

An allelic series of miR-17 ∼ 92-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
Nature genetics | 2015

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.

Pubmed ID: 26029871

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: F31CA168356
  • Agency: NCI NIH HHS, United States
    Id: F31 CA168356
  • Agency: NCI NIH HHS, United States
    Id: R01CA149707
  • Agency: NCI NIH HHS, United States
    Id: P30 CA008748
  • Agency: NCI NIH HHS, United States
    Id: P30CA008748
  • Agency: NCI NIH HHS, United States
    Id: R01 CA149707
  • Agency: NCI NIH HHS, United States
    Id: R01 CA182503

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This is a list of tools and resources that we have found mentioned in this publication.


TargetScan (tool)

RRID:SCR_010845

Web tool to predict biological targets of miRNAs by searching for presence of conserved 8mer, 7mer and 6mer sites that match seed region of each miRNA. Nonconserved sites are also predicted and sites with mismatches in seed region that are compensated by conserved 3' pairing. Used to search for predicted microRNA targets in mammals.

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Circos (tool)

RRID:SCR_011798

A software package for visualizing data and information. It visualizes data in a circular layout - this makes Circos ideal for exploring relationships between objects or positions.

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miRBase (tool)

RRID:SCR_003152

Central online repository for microRNA nomenclature, sequence data, annotation and target prediction.Collection of published miRNA sequences and annotation.

View all literature mentions

Systems Transcriptional Activity Reconstruction (tool)

RRID:SCR_005622

A next-generation web-based application that aims to provide an integrated solution for both visualization and analysis of deep-sequencing data, along with simple access to public datasets.

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

View all literature mentions