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Staufen2-mediated RNA recognition and localization requires combinatorial action of multiple domains

Author

Listed:
  • Simone Heber

    (89081 Ulm University
    Institute of Structural Biology, Helmholtz Zentrum München)

  • Imre Gáspár

    (Developmental Biology Unit, European Molecular Biology Laboratory
    Institute of Molecular Biotechnology)

  • Jan-Niklas Tants

    (Technische Universität München)

  • Johannes Günther

    (Technische Universität München)

  • Sandra M. Fernandez Moya

    (Ludwig-Maximilians-Universität München)

  • Robert Janowski

    (Institute of Structural Biology, Helmholtz Zentrum München)

  • Anne Ephrussi

    (Developmental Biology Unit, European Molecular Biology Laboratory)

  • Michael Sattler

    (Institute of Structural Biology, Helmholtz Zentrum München
    Technische Universität München)

  • Dierk Niessing

    (89081 Ulm University
    Institute of Structural Biology, Helmholtz Zentrum München)

Abstract

Throughout metazoans, Staufen (Stau) proteins are core factors of mRNA localization particles. They consist of three to four double-stranded RNA binding domains (dsRBDs) and a C-terminal dsRBD-like domain. Mouse Staufen2 (mStau2)-like Drosophila Stau (dmStau) contains four dsRBDs. Existing data suggest that only dsRBDs 3–4 are necessary and sufficient for mRNA binding. Here, we show that dsRBDs 1 and 2 of mStau2 bind RNA with similar affinities and kinetics as dsRBDs 3 and 4. While RNA binding by these tandem domains is transient, all four dsRBDs recognize their target RNAs with high stability. Rescue experiments in Drosophila oocytes demonstrate that mStau2 partially rescues dmStau-dependent mRNA localization. In contrast, a rescue with mStau2 bearing RNA-binding mutations in dsRBD1–2 fails, confirming the physiological relevance of our findings. In summary, our data show that the dsRBDs 1–2 play essential roles in the mRNA recognition and function of Stau-family proteins of different species.

Suggested Citation

  • Simone Heber & Imre Gáspár & Jan-Niklas Tants & Johannes Günther & Sandra M. Fernandez Moya & Robert Janowski & Anne Ephrussi & Michael Sattler & Dierk Niessing, 2019. "Staufen2-mediated RNA recognition and localization requires combinatorial action of multiple domains," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09655-3
    DOI: 10.1038/s41467-019-09655-3
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