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HTLV-1 Tax plugs and freezes UPF1 helicase leading to nonsense-mediated mRNA decay inhibition

Author

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  • Francesca Fiorini

    (MMSB-IBCP UMR5086 CNRS, Univ Lyon1
    ENS de Lyon, Univ Claude Bernard Lyon 1, CNRS UMR 5239, INSERM U1210
    PSL Research University)

  • Jean-Philippe Robin

    (ENS de Lyon, Univ Claude Bernard Lyon 1, CNRS UMR 5239, INSERM U1210)

  • Joanne Kanaan

    (PSL Research University)

  • Malgorzata Borowiak

    (ENS de Lyon, Univ Claude Bernard Lyon 1, CNRS UMR 5239, INSERM U1210
    Ludwig-Maximilians-University Munich)

  • Vincent Croquette

    (PSL Research University, Univ Paris Diderot Sorbonne Paris-Cité, Sorbonne Univ UPMC Univ Paris 06, CNRS)

  • Hervé Le Hir

    (PSL Research University)

  • Pierre Jalinot

    (ENS de Lyon, Univ Claude Bernard Lyon 1, CNRS UMR 5239, INSERM U1210)

  • Vincent Mocquet

    (ENS de Lyon, Univ Claude Bernard Lyon 1, CNRS UMR 5239, INSERM U1210)

Abstract

Up-Frameshift Suppressor 1 Homolog (UPF1) is a key factor for nonsense-mediated mRNA decay (NMD), a cellular process that can actively degrade mRNAs. Here, we study NMD inhibition during infection by human T-cell lymphotropic virus type I (HTLV-1) and characterise the influence of the retroviral Tax factor on UPF1 activity. Tax interacts with the central helicase core domain of UPF1 and might plug the RNA channel of UPF1, reducing its affinity for nucleic acids. Furthermore, using a single-molecule approach, we show that the sequential interaction of Tax with a RNA-bound UPF1 freezes UPF1: this latter is less sensitive to the presence of ATP and shows translocation defects, highlighting the importance of this feature for NMD. These mechanistic insights reveal how HTLV-1 hijacks the central component of NMD to ensure expression of its own genome.

Suggested Citation

  • Francesca Fiorini & Jean-Philippe Robin & Joanne Kanaan & Malgorzata Borowiak & Vincent Croquette & Hervé Le Hir & Pierre Jalinot & Vincent Mocquet, 2018. "HTLV-1 Tax plugs and freezes UPF1 helicase leading to nonsense-mediated mRNA decay inhibition," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02793-6
    DOI: 10.1038/s41467-017-02793-6
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