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PDBsum entry 7a6h
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Transcription
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PDB id
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7a6h
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Contents |
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1375 a.a.
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1097 a.a.
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343 a.a.
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124 a.a.
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209 a.a.
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78 a.a.
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189 a.a.
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148 a.a.
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107 a.a.
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66 a.a.
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107 a.a.
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46 a.a.
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220 a.a.
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186 a.a.
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512 a.a.
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146 a.a.
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104 a.a.
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References listed in PDB file
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Key reference
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Title
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Cryo-Em structures of human RNA polymerase III in its unbound and transcribing states.
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Authors
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M.Girbig,
A.D.Misiaszek,
M.K.Vorländer,
A.Lafita,
H.Grötsch,
F.Baudin,
A.Bateman,
C.W.Müller.
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Ref.
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Nat Struct Mol Biol, 2021,
28,
210-219.
[DOI no: ]
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PubMed id
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Abstract
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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.
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