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

Porter, Hayley; Li, Yang; Neguembor, Maria Victoria; Beltran, Manuel; Varsally, Wazeer; Martin, Laura; Tavares Cornejo, Manuel; Pezić, Dubravka; Bhamra, Amandeep; Surinova, Silvia; Jenner, Richard G.; Cosma, Maria Pia; Hadjur, Suzana

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

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dc.contributor.author Porter, Hayley
dc.contributor.author Li, Yang
dc.contributor.author Neguembor, Maria Victoria
dc.contributor.author Beltran, Manuel
dc.contributor.author Varsally, Wazeer
dc.contributor.author Martin, Laura
dc.contributor.author Tavares Cornejo, Manuel
dc.contributor.author Pezić, Dubravka
dc.contributor.author Bhamra, Amandeep
dc.contributor.author Surinova, Silvia
dc.contributor.author Jenner, Richard G.
dc.contributor.author Cosma, Maria Pia
dc.contributor.author Hadjur, Suzana
dc.date.accessioned 2023-06-21T06:34:35Z
dc.date.available 2023-06-21T06:34:35Z
dc.date.issued 2023
dc.description.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 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.
dc.description.sponsorship This work was supported by a Senior Research Fellowship from the Wellcome Trust awarded to SH (106985/Z/15/Z) and a CRUK PhD studentship awarded to HP. The Proteomics work was supported by the CRUK–UCL Centre Award [C416/A25145]. The CLIP work was supported by grants from the European Research Council (ERC, 311704) and Worldwide Cancer Research (21-0255), to RGJ. We are grateful to Jernej Ule for his support with DRIP-sequencing and to Julian Zagalak and the CRICK sequencing facility for reagents, advice and assistance. We thank Stanimir Dulev for his contributions at the early stages of the project and Jiten Manji for his support with microscopy. We also thank Konstantina Skourti-Stathaki for advice about S9.6 antibody, IFs and R-loops. We are grateful to the members of the Hadjur lab for critical discussions and reading of the manuscript.
dc.format.mimetype application/pdf
dc.identifier.citation Porter H, Li Y, Neguembor MV, Beltran M, Varsally W, Martin L, Cornejo MT, Pezić D, Bhamra A, Surinova S, Jenner RG, Cosma MP, Hadjur S. Cohesin-independent STAG proteins interact with RNA and R-loops and promote complex loading. Elife. 2023 Apr 3;12:e79386. DOI: 10.7554/eLife.79386
dc.identifier.doi http://dx.doi.org/10.7554/eLife.79386
dc.identifier.issn 2050-084X
dc.identifier.uri http://hdl.handle.net/10230/57280
dc.language.iso eng
dc.publisher eLife
dc.relation.ispartof Elife. 2023 Apr 3;12:e79386
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/311704
dc.rights © 2023, Porter, Li et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.keyword R-loops
dc.subject.keyword RNA binding proteins
dc.subject.keyword STAG proteins
dc.subject.keyword Cell biology
dc.subject.keyword Chromosomes
dc.subject.keyword Cohesin loading
dc.subject.keyword Gene expression
dc.subject.keyword Human
dc.title Cohesin-independent STAG proteins interact with RNA and R-loops and promote complex loading
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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