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hnRNP H/F drive RNA G-quadruplex-mediated translation linked to genomic instability and therapy resistance in glioblastoma

Author

Listed:
  • Pauline Herviou

    (Cancer Research Center of Toulouse (CRCT), INSERM UMR 1037
    Université Toulouse III Paul Sabatier
    Laboratoire d’Excellence “TOUCAN”)

  • Morgane Le Bras

    (Cancer Research Center of Toulouse (CRCT), INSERM UMR 1037
    Université Toulouse III Paul Sabatier
    Laboratoire d’Excellence “TOUCAN”)

  • Leïla Dumas

    (Cancer Research Center of Toulouse (CRCT), INSERM UMR 1037
    Université Toulouse III Paul Sabatier
    Laboratoire d’Excellence “TOUCAN”)

  • Corinne Hieblot

    (Cancer Research Center of Toulouse (CRCT), INSERM UMR 1037
    Université Toulouse III Paul Sabatier
    Laboratoire d’Excellence “TOUCAN”)

  • Julia Gilhodes

    (Institut Universitaire du Cancer de Toulouse-Oncopole)

  • Gianluca Cioci

    (TBI, Université de Toulouse, CNRS, INRA, INSA)

  • Jean-Philippe Hugnot

    (Université de Montpellier 2)

  • Alfred Ameadan

    (Université de Paris, Inserm U1016-institut Cochin, Labex GReX)

  • François Guillonneau

    (Université de Paris, Inserm U1016-institut Cochin, Labex GReX)

  • Erik Dassi

    (University of Trento Via Sommarive 9)

  • Anne Cammas

    (Cancer Research Center of Toulouse (CRCT), INSERM UMR 1037
    Université Toulouse III Paul Sabatier
    Laboratoire d’Excellence “TOUCAN”)

  • Stefania Millevoi

    (Cancer Research Center of Toulouse (CRCT), INSERM UMR 1037
    Université Toulouse III Paul Sabatier
    Laboratoire d’Excellence “TOUCAN”)

Abstract

RNA G-quadruplexes (RG4s) are four-stranded structures known to control mRNA translation of cancer relevant genes. RG4 formation is pervasive in vitro but not in cellulo, indicating the existence of poorly characterized molecular machinery that remodels RG4s and maintains them unfolded. Here, we performed a quantitative proteomic screen to identify cytosolic proteins that interact with a canonical RG4 in its folded and unfolded conformation. Our results identified hnRNP H/F as important components of the cytoplasmic machinery modulating the structural integrity of RG4s, revealed their function in RG4-mediated translation and uncovered the underlying molecular mechanism impacting the cellular stress response linked to the outcome of glioblastoma.

Suggested Citation

  • Pauline Herviou & Morgane Le Bras & Leïla Dumas & Corinne Hieblot & Julia Gilhodes & Gianluca Cioci & Jean-Philippe Hugnot & Alfred Ameadan & François Guillonneau & Erik Dassi & Anne Cammas & Stefania, 2020. "hnRNP H/F drive RNA G-quadruplex-mediated translation linked to genomic instability and therapy resistance in glioblastoma," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16168-x
    DOI: 10.1038/s41467-020-16168-x
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    Cited by:

    1. Geng Liu & Wenya Du & Xiongbo Sang & Qiyu Tong & Ye Wang & Guoqing Chen & Yi Yuan & Lili Jiang & Wei Cheng & Dan Liu & Yan Tian & Xianghui Fu, 2022. "RNA G-quadruplex in TMPRSS2 reduces SARS-CoV-2 infection," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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