7AST

Apo Human RNA Polymerase III

Summary for 7AST

• Entry DOI: 10.2210/pdb7ast/pdb
• EMDB information: 11904
• Descriptor: DNA-directed RNA polymerase III subunit RPC1, DNA-directed RNA polymerase III subunit RPC9, DNA-directed RNA polymerase III subunit RPC8, ... (17 entities in total)
• Functional Keywords: rna polymerase iii, trna, transcription
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 17
• Total formula weight: 685449.90

Authors

Ramsay, E.P.,Abascal-Palacios, G.,Daiss, J.L.,King, H.,Gouge, J.,Pilsl, M.,Beuron, F.,Morris, E.,Gunkel, P.,Engel, C.,Vannini, A. (deposition date: 2020-10-28, release date: 2020-12-23, Last modification date: 2020-12-30)

Primary citation

Ramsay, E.P.,Abascal-Palacios, G.,Daiss, J.L.,King, H.,Gouge, J.,Pilsl, M.,Beuron, F.,Morris, E.,Gunkel, P.,Engel, C.,Vannini, A.
Structure of human RNA polymerase III.
Nat Commun, 11:6409-6409, 2020

PubMed 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.

PubMed: 33335104
DOI: 10.1038/s41467-020-20262-5

Experimental method

ELECTRON MICROSCOPY (4 Å)