A combinatorial approach to uncover an additional Integrator subunit

• DOI: 10.1016/j.celrep.2023.112244
• Publication Date: 2023-03-14T04:26:35Z
• Authors: Sarah R. Offley; Moritz M. Pfleiderer; Avery Zucco; Angelique Fraudeau; Sarah A. Welsh; Michal Razew; Wojciech P. Galej; Alessandro Gardini
• Keywords: RNA polymerase II; Transcription; Functional Genomics

RNA polymerase II (RNAPII) controls expression of all protein-coding genes and most noncoding loci in higher eukaryotes. Calibrating RNAPII activity requires an assortment polymerase-associated factors that are recruited at sites active transcription. The Integrator complex is one the elusive transcriptional regulators metazoans, deemed to be after initiation help establish modulate paused RNAPII. known composed 14 subunits assemble operate a modular fashion. We employed proteomics machine-learning structure prediction (AlphaFold2) identify additional subunit, INTS15. report INTS15 assembles primarily with INTS13/14/10 module interfaces Int-PP2A module. Functional genomics analysis further reveals role for modulating pausing subset genes. Our study shows omics approaches combined AlphaFold2-based predictions provide insights into molecular architecture large dynamic multiprotein complexes.