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TitleStructural basis of Integrator-dependent RNA polymerase II termination.
Journal, issue, pagesNature, Year 2024
Publish dateApr 3, 2024
AuthorsIsaac Fianu / Moritz Ochmann / James L Walshe / Olexandr Dybkov / Joseph Neos Cruz / Henning Urlaub / Patrick Cramer /
PubMed AbstractThe Integrator complex can terminate RNA polymerase II (Pol II) in the promoter-proximal region of genes. Previous work has shed light on how Integrator binds to the paused elongation complex ...The Integrator complex can terminate RNA polymerase II (Pol II) in the promoter-proximal region of genes. Previous work has shed light on how Integrator binds to the paused elongation complex consisting of Pol II, the DRB sensitivity-inducing factor (DSIF) and the negative elongation factor (NELF) and how it cleaves the nascent RNA transcript, but has not explained how Integrator removes Pol II from the DNA template. Here we present three cryo-electron microscopy structures of the complete Integrator-PP2A complex in different functional states. The structure of the pre-termination complex reveals a previously unresolved, scorpion-tail-shaped INTS10-INTS13-INTS14-INTS15 module that may use its 'sting' to open the DSIF DNA clamp and facilitate termination. The structure of the post-termination complex shows that the previously unresolved subunit INTS3 and associated sensor of single-stranded DNA complex (SOSS) factors prevent Pol II rebinding to Integrator after termination. The structure of the free Integrator-PP2A complex in an inactive closed conformation reveals that INTS6 blocks the PP2A phosphatase active site. These results lead to a model for how Integrator terminates Pol II transcription in three steps that involve major rearrangements.
External linksNature / PubMed:38570683
MethodsEM (single particle)
Resolution3.1 - 4.1 Å
Structure data

19038

8rbx

EMDB-19038, PDB-8rbx:
Structure of Integrator-PP2A bound to a paused RNA polymerase II-DSIF-NELF-nucleosome complex
Method: EM (single particle) / Resolution: 4.1 Å

19040

8rbz

EMDB-19040, PDB-8rbz:
Structure of Integrator-PP2A-SOSS-CTD post-termination complex
Method: EM (single particle) / Resolution: 3.7 Å

19047

8rc4

EMDB-19047, PDB-8rc4:
Structure of Integrator-PP2A complex
Method: EM (single particle) / Resolution: 3.1 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-MG:
Unknown entry

ChemComp-MN:
Unknown entry

Source
  • homo sapiens (human)
  • sus scrofa (pig)
  • trichoplusia ni (cabbage looper)
  • synthetic construct (others)
KeywordsTRANSCRIPTION / Integrator complex / Pre-termination complex / Post-termination complex / RNA Polymerase II / Pol II / RNAPII

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