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Title | Structural basis of the Integrator complex assembly and association with transcription factors. |
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Journal, issue, pages | Mol Cell, Vol. 84, Issue 13, Page 2542-22552.e5, Year 2024 |
Publish date | Jul 11, 2024 |
![]() | Michal Razew / Angelique Fraudeau / Moritz M Pfleiderer / Romain Linares / Wojciech P Galej / ![]() |
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 ...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. |
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Methods | EM (single particle) |
Resolution | 3.2 - 7.7 Å |
Structure data | EMDB-19851, PDB-9eoc: EMDB-19853, PDB-9eof: EMDB-19871, PDB-9ep1: EMDB-19872, PDB-9ep4: EMDB-50267, PDB-9fa4: EMDB-50268, PDB-9fa7: |
Chemicals | ![]() ChemComp-MG: |
Source |
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![]() | TRANSCRIPTION / Integrator complex assembly / RNA polymerase II transcription termination / transcription factors / Integrator complex |