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TitleCryo-EM structures of human RNA polymerase III in its unbound and transcribing states.
Journal, issue, pagesNat Struct Mol Biol, Vol. 28, Issue 2, Page 210-219, Year 2021
Publish dateFeb 8, 2021
AuthorsMathias Girbig / Agata D Misiaszek / Matthias K Vorländer / Aleix Lafita / Helga Grötsch / Florence Baudin / Alex Bateman / Christoph W Müller /
PubMed AbstractRNA polymerase III (Pol III) synthesizes transfer RNAs and other short, essential RNAs. Human Pol III misregulation is linked to tumor transformation, neurodegenerative and developmental disorders, ...RNA polymerase III (Pol III) synthesizes transfer RNAs and other short, essential RNAs. Human Pol III misregulation is linked to tumor transformation, neurodegenerative and developmental disorders, and increased sensitivity to viral infections. Here, we present cryo-electron microscopy structures at 2.8 to 3.3 Å resolution of transcribing and unbound human Pol III. We observe insertion of the TFIIS-like subunit RPC10 into the polymerase funnel, providing insights into how RPC10 triggers transcription termination. Our structures resolve elements absent from Saccharomyces cerevisiae Pol III such as the winged-helix domains of RPC5 and an iron-sulfur cluster, which tethers the heterotrimer subcomplex to the core. The cancer-associated RPC7α isoform binds the polymerase clamp, potentially interfering with Pol III inhibition by tumor suppressor MAF1, which may explain why overexpressed RPC7α enhances tumor transformation. Finally, the human Pol III structure allows mapping of disease-related mutations and may contribute to the development of inhibitors that selectively target Pol III for therapeutic interventions.
External linksNat Struct Mol Biol / PubMed:33558764 / PubMed Central
MethodsEM (single particle)
Resolution2.8 - 3.4 Å
Structure data

EMDB-11673, PDB-7a6h:
Cryo-EM structure of human apo RNA Polymerase III
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-11736, PDB-7ae1:
Cryo-EM structure of human RNA Polymerase III elongation complex 1
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-11737:
Human RNA Polymerase III Elongation Complex, Map C
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-11738, PDB-7ae3:
Cryo-EM structure of human RNA Polymerase III elongation complex 3
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-11739:
Cryo-EM structure of human RNA Polymerase III Elongation Complex, Map E
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-11740:
Cryo-EM structure of human RNA Polymerase III Elongation Complex, map F
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-11741:
Cryo-EM structure of human RNA Polymerase III, map G
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-11742, PDB-7aea:
Cryo-EM structure of human RNA Polymerase III elongation complex 2
Method: EM (single particle) / Resolution: 3.4 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-MG:
Unknown entry

ChemComp-SF4:
IRON/SULFUR CLUSTER / Iron–sulfur cluster

Source
  • homo sapiens (human)
  • synthetic construct (others)
KeywordsTRANSCRIPTION / Human RNA polymerase III / Synthesis of short RNAs / apo complex / HUMAN / SHORT RNAs

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