9EP4

Structure of Integrator subcomplex INTS5/8/15

Summary for 9EP4

• Entry DOI: 10.2210/pdb9ep4/pdb
• EMDB information: 19872
• Descriptor: Integrator complex subunit 8, Integrator complex subunit 5, Integrator complex subunit 15 (3 entities in total)
• Functional Keywords: rna polymerase ii transcription termination, integrator complex assembly, transcription factors, transcription
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 271437.49

Authors

Razew, M.,Galej, W.P. (deposition date: 2024-03-17, release date: 2024-06-12, Last modification date: 2024-07-24)

Primary citation

Razew, M.,Fraudeau, A.,Pfleiderer, M.M.,Linares, R.,Galej, W.P.
Structural basis of the Integrator complex assembly and association with transcription factors.
Mol.Cell, 84:2542-, 2024

PubMed Abstract: Integrator is a multi-subunit protein complex responsible for premature transcription termination of coding and non-coding RNAs. This is achieved via two enzymatic activities, RNA endonuclease and protein phosphatase, acting on the promoter-proximally paused RNA polymerase Ⅱ (RNAPⅡ). Yet, it remains unclear how Integrator assembly and recruitment are regulated and what the functions of many of its core subunits are. Here, we report the structures of two human Integrator sub-complexes: INTS10/13/14/15 and INTS5/8/10/15, and an integrative model of the fully assembled Integrator bound to the RNAPⅡ paused elongating complex (PEC). An in silico protein-protein interaction screen of over 1,500 human transcription factors (TFs) identified ZNF655 as a direct interacting partner of INTS13 within the fully assembled Integrator. We propose a model wherein INTS13 acts as a platform for the recruitment of TFs that could modulate the stability of the Integrator's association at specific loci and regulate transcription attenuation of the target genes.

PubMed: 38823386
DOI: 10.1016/j.molcel.2024.05.009

Experimental method

ELECTRON MICROSCOPY (3.2 Å)