BIROn - Birkbeck Institutional Research Online

    Structure of human RNA polymerase III

    Ramsay, E.P. and Abascal-Palacios, G. and Daiß, J.L. and King, H. and Gouge, Jerome and Pilsl, M. and Beuron, F. and Morris, E. and Gunkel, P. and Engel, C. and Vannini, A. (2020) Structure of human RNA polymerase III. Nature Communications 11 (6409), ISSN 2041-1723.

    [img]
    Preview
    Text
    41467_2020_Article_20262.pdf - Published Version of Record
    Available under License Creative Commons Attribution.

    Download (5MB) | Preview

    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.

    Metadata

    Item Type: Article
    School: School of Science > Biological Sciences
    Research Centres and Institutes: Structural Molecular Biology, Institute of (ISMB)
    Depositing User: Jerome Gouge
    Date Deposited: 12 Jan 2021 16:06
    Last Modified: 10 Feb 2021 21:03
    URI: https://eprints.bbk.ac.uk/id/eprint/42478

    Statistics

    Downloads
    Activity Overview
    3Downloads
    26Hits

    Additional statistics are available via IRStats2.

    Archive Staff Only (login required)

    Edit/View Item Edit/View Item