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The RNA helicase DHX34 functions as a scaffold for SMG1-mediated UPF1 phosphorylation

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  • Roberto Melero

    (Centro de Investigaciones Biológicas (CIB), Consejo Superior de Investigaciones Científicas (Spanish National Research Council, CSIC)
    Present address: Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (Spanish National Research Council, CSIC), Darwin 3, Madrid 28049, Spain)

  • Nele Hug

    (MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh)

  • Andrés López-Perrote

    (Centro de Investigaciones Biológicas (CIB), Consejo Superior de Investigaciones Científicas (Spanish National Research Council, CSIC))

  • Akio Yamashita

    (Yokohama City University School of Medicine)

  • Javier F. Cáceres

    (MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh)

  • Oscar Llorca

    (Centro de Investigaciones Biológicas (CIB), Consejo Superior de Investigaciones Científicas (Spanish National Research Council, CSIC))

Abstract

Nonsense-mediated decay (NMD) is a messenger RNA quality-control pathway triggered by SMG1-mediated phosphorylation of the NMD factor UPF1. In recent times, the RNA helicase DHX34 was found to promote mRNP remodelling, leading to activation of NMD. Here we demonstrate the mechanism by which DHX34 functions in concert with SMG1. DHX34 comprises two distinct structural units, a core that binds UPF1 and a protruding carboxy-terminal domain (CTD) that binds the SMG1 kinase, as shown using truncated forms of DHX34 and electron microscopy of the SMG1–DHX34 complex. Truncation of the DHX34 CTD does not affect binding to UPF1; however, it compromises DHX34 binding to SMG1 to affect UPF1 phosphorylation and hence abrogate NMD. Altogether, these data suggest the existence of a complex comprising SMG1, UPF1 and DHX34, with DHX34 functioning as a scaffold for UPF1 and SMG1. This complex promotes UPF1 phosphorylation leading to functional NMD.

Suggested Citation

  • Roberto Melero & Nele Hug & Andrés López-Perrote & Akio Yamashita & Javier F. Cáceres & Oscar Llorca, 2016. "The RNA helicase DHX34 functions as a scaffold for SMG1-mediated UPF1 phosphorylation," Nature Communications, Nature, vol. 7(1), pages 1-12, April.
  • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10585
    DOI: 10.1038/ncomms10585
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