Cryo-EM structures of human RNA polymerase III in its unbound and transcribing states.
Journal
Nature structural & molecular biology
ISSN: 1545-9985
Titre abrégé: Nat Struct Mol Biol
Pays: United States
ID NLM: 101186374
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
27
06
2020
accepted:
21
12
2020
pubmed:
10
2
2021
medline:
1
4
2021
entrez:
9
2
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33558764
doi: 10.1038/s41594-020-00555-5
pii: 10.1038/s41594-020-00555-5
pmc: PMC7610652
mid: EMS114681
doi:
Substances chimiques
RNA Polymerase III
EC 2.7.7.6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
210-219Commentaires et corrections
Type : CommentIn
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