TY - JOUR TI - Cohesin-independent STAG proteins interact with RNA and R-loops and promote complex loading AU - Porter, Hayley AU - Li, Yang AU - Neguembor, Maria Victoria AU - Beltran, Manuel AU - Varsally, Wazeer AU - Martin, Laura AU - Cornejo, Manuel Tavares AU - Pezić, Dubravka AU - Bhamra, Amandeep AU - Surinova, Silvia AU - Jenner, Richard G AU - Cosma, Maria Pia AU - Hadjur, Suzana A2 - Aguilera, Andrés A2 - Struhl, Kevin A2 - Vannini, Alessandro VL - 12 PY - 2023 DA - 2023/04/03 SP - e79386 C1 - eLife 2023;12:e79386 DO - 10.7554/eLife.79386 UR - https://doi.org/10.7554/eLife.79386 AB - Most studies of cohesin function consider the Stromalin Antigen (STAG/SA) proteins as core complex members given their ubiquitous interaction with the cohesin ring. Here, we provide functional data to support the notion that the SA subunit is not a mere passenger in this structure, but instead plays a key role in the localization of cohesin to diverse biological processes and promotes loading of the complex at these sites. We show that in cells acutely depleted for RAD21, SA proteins remain bound to chromatin, cluster in 3D and interact with CTCF, as well as with a wide range of RNA binding proteins involved in multiple RNA processing mechanisms. Accordingly, SA proteins interact with RNA, and R-loops, even in the absence of cohesin. Our results place SA1 on chromatin upstream of the cohesin ring and reveal a role for SA1 in cohesin loading which is independent of NIPBL, the canonical cohesin loader. We propose that SA1 takes advantage of structural R-loop platforms to link cohesin loading and chromatin structure with diverse functions. Since SA proteins are pan-cancer targets, and R-loops play an increasingly prevalent role in cancer biology, our results have important implications for the mechanistic understanding of SA proteins in cancer and disease. KW - STAG proteins KW - RNA binding proteins KW - R-loops KW - cohesin loading JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -