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Cohesin-independent STAG proteins interact with RNA and localise to R-loops to promote complex loading

Porter, Hayley; Li, Yang; Neguembor, Maria Victoria; Beltran, Manuel; Varsally, Wazeer; Martin, Laura; Cornejo, Manuel Tavares; ... Hadjur, Suzana; + view all (2023) Cohesin-independent STAG proteins interact with RNA and localise to R-loops to promote complex loading. bioRxiv: Cold Spring Harbor, NY, USA. Green open access

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Abstract

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 are localised to R-loops where they contribute to R-loop regulation. Our results place SA1 within R-loop domains upstream of the cohesin complex 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.

Type: Working / discussion paper
Title: Cohesin-independent STAG proteins interact with RNA and localise to R-loops to promote complex loading
Open access status: An open access version is available from UCL Discovery
DOI: 10.1101/2021.02.20.432055
Publisher version: https://doi.org/10.1101/2021.02.20.432055
Language: English
Additional information: The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Cohesin, STAG proteins, R-loops, genome organization
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: https://discovery.ucl.ac.uk/id/eprint/10167724
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