Ramsay, Ewan Phillip and Abascal-Palacios, Guillermo and Daiss, Julia L. and King, Helen and Gouge, Jerome and Pilsl, Michael and Beuron, Fabienne and Morris, Edward and Gunkel, Philip and Engel, Christoph and Vannini, Alessandro (2020) Structure of human RNA polymerase III. NATURE COMMUNICATIONS, 11 (1): 6409. ISSN 2041-1723,
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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 angstrom 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. The eukaryotic RNA Polymerase III transcribes tRNAs, some ribosomal and spliceosomal RNAs. Here, the authors resolve a cryo-EM structure of human RNA Polymerase III in its apo form and complemented it with crystal structures and SAXS analysis of RPC5, revealing insights into the molecular mechanisms of Pol III transcription.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | COMPOUND HETEROZYGOUS MUTATIONS; TRANSCRIPTION INITIATION; BIOLOGICAL MACROMOLECULES; SOLUTION SCATTERING; CATALYTIC SUBUNIT; 4H SYNDROME; POL III; VISUALIZATION; PREDICTION; MECHANISM; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 04 Mar 2021 13:37 |
| Last Modified: | 04 Mar 2021 13:37 |
| URI: | https://pred.uni-regensburg.de/id/eprint/43122 |
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