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TitleStructure of human RNA polymerase III.
Journal, issue, pagesNat Commun, Vol. 11, Issue 1, Page 6409, Year 2020
Publish dateDec 17, 2020
AuthorsEwan Phillip Ramsay / Guillermo Abascal-Palacios / Julia L Daiß / Helen King / Jerome Gouge / Michael Pilsl / Fabienne Beuron / Edward Morris / Philip Gunkel / Christoph Engel / Alessandro Vannini /
PubMed AbstractIn 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. ...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.
External linksNat Commun / PubMed:33335104 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.55 - 4.0 Å
Structure data

11904

7ast

EMDB-11904, PDB-7ast:
Apo Human RNA Polymerase III
Method: EM (single particle) / Resolution: 4.0 Å

PDB-7asu:
Crystal structure of tWHD1 of Rpc5 subunit of human RNA Polymerase III
Method: X-RAY DIFFRACTION / Resolution: 2.23 Å

PDB-7asv:
Crystal structure of tWHD2 of Rpc5 subunit of human RNA Polymerase III
Method: X-RAY DIFFRACTION / Resolution: 1.55 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-HOH:
WATER / Water

ChemComp-ACT:
ACETATE ION / Acetate

Source
  • homo sapiens (human)
  • Human (human)
KeywordsTRANSCRIPTION / RNA Polymerase III / tRNA / RNA Pol III / Rpc5

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