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HuR and miR-1192 regulate myogenesis by modulating the translation of HMGB1 mRNA

Author

Listed:
  • Virginie Dormoy-Raclet

    (McGill University, Goodman Cancer Center)

  • Anne Cammas

    (McGill University, Goodman Cancer Center)

  • Barbara Celona

    (San Raffaele University and Scientific Institute)

  • Xian Jin Lian

    (McGill University, Goodman Cancer Center)

  • Kate van der Giessen

    (McGill University, Goodman Cancer Center)

  • Marija Zivojnovic

    (McGill University, Goodman Cancer Center)

  • Silvia Brunelli

    (University of Milan-Bicocca
    San Raffaele Scientific Institute, Stem Cells and Gene Therapy)

  • Francesca Riuzzi

    (University of Perugia)

  • Guglielmo Sorci

    (University of Perugia)

  • Brian T. Wilhelm

    (Institute for Research in Immunology and Cancer (IRIC), Université de Montréal)

  • Sergio Di Marco

    (McGill University, Goodman Cancer Center)

  • Rosario Donato

    (University of Perugia)

  • Marco E. Bianchi

    (San Raffaele University and Scientific Institute)

  • Imed-Eddine Gallouzi

    (McGill University, Goodman Cancer Center)

Abstract

Upon muscle injury, the high mobility group box 1 (HMGB1) protein is upregulated and secreted to initiate reparative responses. Here we show that HMGB1 controls myogenesis both in vitro and in vivo during development and after adult muscle injury. HMGB1 expression in muscle cells is regulated at the translational level: the miRNA miR-1192 inhibits HMGB1 translation and the RNA-binding protein HuR promotes it. HuR binds to a cis-element, HuR binding sites (HuRBS), located in the 3′UTR of the HMGB1 transcript, and at the same time miR-1192 is recruited to an adjacent seed element. The binding of HuR to the HuRBS prevents the recruitment of Argonaute 2 (Ago2), overriding miR-1192-mediated translation inhibition. Depleting HuR reduces myoblast fusion and silencing miR-1192 re-establishes the fusion potential of HuR-depleted cells. We propose that HuR promotes the commitment of myoblasts to myogenesis by enhancing the translation of HMGB1 and suppressing the translation inhibition mediated by miR-1192.

Suggested Citation

  • Virginie Dormoy-Raclet & Anne Cammas & Barbara Celona & Xian Jin Lian & Kate van der Giessen & Marija Zivojnovic & Silvia Brunelli & Francesca Riuzzi & Guglielmo Sorci & Brian T. Wilhelm & Sergio Di M, 2013. "HuR and miR-1192 regulate myogenesis by modulating the translation of HMGB1 mRNA," Nature Communications, Nature, vol. 4(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3388
    DOI: 10.1038/ncomms3388
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