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.
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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: | Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences |
| Research Centres and Institutes: | Structural Molecular Biology, Institute of (ISMB) |
| Depositing User: | Jerome Gouge |
| Date Deposited: | 12 Jan 2021 16:06 |
| Last Modified: | 02 Aug 2023 18:06 |
| URI: | https://eprints.bbk.ac.uk/id/eprint/42478 |
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