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A transgenic resource for conditional competitive inhibition of conserved Drosophila microRNAs

Author

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  • Tudor A. Fulga

    (Harvard Medical School
    Present addresses: Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK)

  • Elizabeth M. McNeill

    (Harvard Medical School)

  • Richard Binari

    (Harvard Medical School
    Howard Hughes Medical Institute)

  • Julia Yelick

    (Harvard Medical School)

  • Alexandra Blanche

    (Harvard Medical School)

  • Matthew Booker

    (Harvard Medical School)

  • Bruno R. Steinkraus

    (Weatherall Institute of Molecular Medicine, University of Oxford)

  • Michael Schnall-Levin

    (Harvard Medical School)

  • Yong Zhao

    (Harvard Medical School)

  • Todd DeLuca

    (Harvard Medical School)

  • Fernando Bejarano

    (Sloan-Kettering Institute)

  • Zhe Han

    (Center for Cancer and Immunology Research, Children’s Research Institute, Children’s National Medical Center)

  • Eric C. Lai

    (Sloan-Kettering Institute)

  • Dennis P. Wall

    (Harvard Medical School
    Present addresses: Department of Pediatrics, Division of Systems Medicine, Stanford University, Palo Alto, California 94305, USA)

  • Norbert Perrimon

    (Harvard Medical School
    Howard Hughes Medical Institute)

  • David Van Vactor

    (Harvard Medical School)

Abstract

Although the impact of microRNAs (miRNAs) in development and disease is well established, understanding the function of individual miRNAs remains challenging. Development of competitive inhibitor molecules such as miRNA sponges has allowed the community to address individual miRNA function in vivo. However, the application of these loss-of-function strategies has been limited. Here we offer a comprehensive library of 141 conditional miRNA sponges targeting well-conserved miRNAs in Drosophila. Ubiquitous miRNA sponge delivery and consequent systemic miRNA inhibition uncovers a relatively small number of miRNA families underlying viability and gross morphogenesis, with false discovery rates in the 4–8% range. In contrast, tissue-specific silencing of muscle-enriched miRNAs reveals a surprisingly large number of novel miRNA contributions to the maintenance of adult indirect flight muscle structure and function. A strong correlation between miRNA abundance and physiological relevance is not observed, underscoring the importance of unbiased screens when assessing the contributions of miRNAs to complex biological processes.

Suggested Citation

  • Tudor A. Fulga & Elizabeth M. McNeill & Richard Binari & Julia Yelick & Alexandra Blanche & Matthew Booker & Bruno R. Steinkraus & Michael Schnall-Levin & Yong Zhao & Todd DeLuca & Fernando Bejarano &, 2015. "A transgenic resource for conditional competitive inhibition of conserved Drosophila microRNAs," Nature Communications, Nature, vol. 6(1), pages 1-10, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8279
    DOI: 10.1038/ncomms8279
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