Structure of human RNA polymerase III.
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Authors
Ramsay, EP
Abascal-Palacios, G
Daiß, JL
King, H
Gouge, J
Pilsl, M
Beuron, F
Morris, E
Gunkel, P
Engel, C
Vannini, A
Abascal-Palacios, G
Daiß, JL
King, H
Gouge, J
Pilsl, M
Beuron, F
Morris, E
Gunkel, P
Engel, C
Vannini, A
Document Type
Journal Article
Date
2020-12-17
Date Accepted
2020-11-20
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.
Citation
Nature communications, 2020, 11 (1), pp. 6409 - ?
Source Title
Publisher
NATURE PORTFOLIO
ISSN
2041-1723
eISSN
2041-1723
Collections
Research Team
Structural Electron Microscopy
Vannini Group
Vannini Group