Ramsay, Ewan Phillip;
Abascal-Palacios, Guillermo;
Daiss, Julia L;
King, Helen;
Gouge, Jerome;
Pilsl, Michael;
Beuron, Fabienne;
... Vannini, Alessandro; + view all
(2020)
Structure of human RNA polymerase III.
Nature Communications
, 11
(1)
, Article 6409. 10.1038/s41467-020-20262-5.
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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.
| Type: | Article |
|---|---|
| Title: | Structure of human RNA polymerase III |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41467-020-20262-5 |
| Publisher version: | https://doi.org/10.1038/s41467-020-20262-5 |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, COMPOUND HETEROZYGOUS MUTATIONS, TRANSCRIPTION INITIATION, BIOLOGICAL MACROMOLECULES, SOLUTION SCATTERING, CATALYTIC SUBUNIT, 4H SYNDROME, POL III, VISUALIZATION, PREDICTION, MECHANISM |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10164802 |
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