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Structure of human RNA polymerase III

DOI: 10.1038/s41467-020-20262-5 DOI Help

Authors: Ewan Phillip Ramsay (The Institute of Cancer Research) , Guillermo Abascal-Palacios (The Institute of Cancer Research) , Julia L. Daiß (University of Regensburg) , Helen King (The Institute of Cancer Research) , Jerome Gouge (The Institute of Cancer Research) , Michael Pilsl (University of Regensburg) , Fabienne Beuron (The Institute of Cancer Research) , Edward Morris (The Institute of Cancer Research) , Philip Gunkel (Max Planck Institute for Biophysical Chemistry) , Christoph Engel (University of Regensburg) , Alessandro Vannini (The Institute of Cancer Research; Fondazione Human Technopole)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 11

State: Published (Approved)
Published: December 2020
Diamond Proposal Number(s): 8015 , 10088

Open Access Open Access

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.

Journal Keywords: CRISPR-Cas9 genome editing; Cryoelectron microscopy; SAXS; Transcription; X-ray crystallography

Subject Areas: Biology and Bio-materials

Instruments: I24-Microfocus Macromolecular Crystallography

Added On: 06/01/2021 08:40


Discipline Tags:

Life Sciences & Biotech Genetics Health & Wellbeing Drug Discovery Structural biology Chemistry Biochemistry

Technical Tags:

Diffraction Macromolecular Crystallography (MX)