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Roquin binds microRNA-146a and Argonaute2 to regulate microRNA homeostasis

Author

Listed:
  • Monika Srivastava

    (John Curtin School of Medical Research)

  • Guowen Duan

    (John Curtin School of Medical Research)

  • Nadia J. Kershaw

    (Walter and Eliza Hall Institute and The University of Melbourne)

  • Vicki Athanasopoulos

    (John Curtin School of Medical Research)

  • Janet H. C. Yeo

    (Genomics and Immunology laboratory, St Vincent’s Institute of Medical Research)

  • Toyoyuki Ose

    (Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive)

  • Desheng Hu

    (Helmholtz Zentrum München, Institute of Molecular Immunology)

  • Simon H. J. Brown

    (Centre for Medical and Molecular Bioscience, University of Wollongong and Illawarra Health and Medical Research Institute)

  • Slobodan Jergic

    (Centre for Medical and Molecular Bioscience, University of Wollongong and Illawarra Health and Medical Research Institute)

  • Hardip R. Patel

    (John Curtin School of Medical Research
    Genome Discovery Unit, John Curtin School of Medical Research)

  • Alvin Pratama

    (John Curtin School of Medical Research)

  • Sashika Richards

    (John Curtin School of Medical Research)

  • Anil Verma

    (Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive)

  • E. Yvonne Jones

    (Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive)

  • Vigo Heissmeyer

    (Helmholtz Zentrum München, Institute of Molecular Immunology
    Ludwig-Maximilians-Universität München, Institute for Immunology)

  • Thomas Preiss

    (John Curtin School of Medical Research
    Victor Chang Cardiac Research Institute)

  • Nicholas E. Dixon

    (Centre for Medical and Molecular Bioscience, University of Wollongong and Illawarra Health and Medical Research Institute)

  • Mark M. W. Chong

    (Genomics and Immunology laboratory, St Vincent’s Institute of Medical Research)

  • Jeffrey J. Babon

    (Walter and Eliza Hall Institute and The University of Melbourne)

  • Carola G. Vinuesa

    (John Curtin School of Medical Research)

Abstract

Roquin is an RNA-binding protein that prevents autoimmunity and inflammation via repression of bound target mRNAs such as inducible costimulator (Icos). When Roquin is absent or mutated (Roquinsan), Icos is overexpressed in T cells. Here we show that Roquin enhances Dicer-mediated processing of pre-miR-146a. Roquin also directly binds Argonaute2, a central component of the RNA-induced silencing complex, and miR-146a, a microRNA that targets Icos mRNA. In the absence of functional Roquin, miR-146a accumulates in T cells. Its accumulation is not due to increased transcription or processing, rather due to enhanced stability of mature miR-146a. This is associated with decreased 3′ end uridylation of the miRNA. Crystallographic studies reveal that Roquin contains a unique HEPN domain and identify the structural basis of the ‘san’ mutation and Roquin’s ability to bind multiple RNAs. Roquin emerges as a protein that can bind Ago2, miRNAs and target mRNAs, to control homeostasis of both RNA species.

Suggested Citation

  • Monika Srivastava & Guowen Duan & Nadia J. Kershaw & Vicki Athanasopoulos & Janet H. C. Yeo & Toyoyuki Ose & Desheng Hu & Simon H. J. Brown & Slobodan Jergic & Hardip R. Patel & Alvin Pratama & Sashik, 2015. "Roquin binds microRNA-146a and Argonaute2 to regulate microRNA homeostasis," Nature Communications, Nature, vol. 6(1), pages 1-13, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7253
    DOI: 10.1038/ncomms7253
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