8RBZ

Structure of Integrator-PP2A-SOSS-CTD post-termination complex

Summary for 8RBZ

• Entry DOI: 10.2210/pdb8rbz/pdb
• EMDB information: 19040
• Descriptor: UNK-UNK-UNK-UNK-UNK-UNK-UNK-UNK-UNK, Integrator complex subunit 6, Integrator complex subunit 7, ... (23 entities in total)
• Functional Keywords: integrator complex, post-termination complex, rna polymerase ii, pol ii, rnapii, transcription
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 21
• Total formula weight: 1588875.02

Authors

Fianu, I.,Ochmann, M.,Walshe, J.L.,Cramer, P. (deposition date: 2023-12-05, release date: 2024-02-07, Last modification date: 2024-05-15)

Primary citation

Fianu, I.,Ochmann, M.,Walshe, J.L.,Dybkov, O.,Cruz, J.N.,Urlaub, H.,Cramer, P.
Structural basis of Integrator-dependent RNA polymerase II termination.
Nature, 629:219-227, 2024

PubMed Abstract: 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.

PubMed: 38570683
DOI: 10.1038/s41586-024-07269-4

Experimental method

ELECTRON MICROSCOPY (3.7 Å)