9ep1

Publication Abstract from PubMed

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.

Structural basis of the Integrator complex assembly and association with transcription factors.,Razew M, Fraudeau A, Pfleiderer MM, Linares R, Galej WP Mol Cell. 2024 May 27:S1097-2765(24)00431-3. doi: 10.1016/j.molcel.2024.05.009. PMID:38823386^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.