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Structure of human RNA polymerase III

Author

Listed:
  • Ewan Phillip Ramsay

    (The Institute of Cancer Research)

  • Guillermo Abascal-Palacios

    (The Institute of Cancer Research)

  • Julia L. Daiß

    (University of Regensburg)

  • Helen King

    (The Institute of Cancer Research)

  • Jerome Gouge

    (The Institute of Cancer Research)

  • Michael Pilsl

    (University of Regensburg)

  • Fabienne Beuron

    (The Institute of Cancer Research)

  • Edward Morris

    (The Institute of Cancer Research)

  • Philip Gunkel

    (Research Group Nuclear Architecture)

  • Christoph Engel

    (University of Regensburg)

  • Alessandro Vannini

    (The Institute of Cancer Research
    Structural Biology Research Centre)

Abstract

In eukaryotes, RNA Polymerase (Pol) III is specialized for the transcription of tRNAs and other short, untranslated RNAs. Pol III is a determinant of cellular growth and lifespan across eukaryotes. Upregulation of Pol III transcription is observed in cancer and causative Pol III mutations have been described in neurodevelopmental disorders and hypersensitivity to viral infection. Here, we report a cryo-EM reconstruction at 4.0 Å of human Pol III, allowing mapping and rationalization of reported genetic mutations. Mutations causing neurodevelopmental defects cluster in hotspots affecting Pol III stability and/or biogenesis, whereas mutations affecting viral sensing are located in proximity to DNA binding regions, suggesting an impairment of Pol III cytosolic viral DNA-sensing. Integrating x-ray crystallography and SAXS, we also describe the structure of the higher eukaryote specific RPC5 C-terminal extension. Surprisingly, experiments in living cells highlight a role for this module in the assembly and stability of human Pol III.

Suggested Citation

  • Ewan Phillip Ramsay & Guillermo Abascal-Palacios & Julia L. Daiß & Helen King & Jerome Gouge & Michael Pilsl & Fabienne Beuron & Edward Morris & Philip Gunkel & Christoph Engel & Alessandro Vannini, 2020. "Structure of human RNA polymerase III," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-20262-5
    DOI: 10.1038/s41467-020-20262-5
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