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

Autor:	Porter H; Research Department of Cancer Biology, Cancer Institute, University College London, London, United Kingdom., Li Y; Research Department of Cancer Biology, Cancer Institute, University College London, London, United Kingdom., Neguembor MV; Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Barcelona, Spain., Beltran M; Regulatory Genomics Group, Cancer Institute, University College London, London, United Kingdom., Varsally W; Research Department of Cancer Biology, Cancer Institute, University College London, London, United Kingdom., Martin L; Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Barcelona, Spain., Cornejo MT; Regulatory Genomics Group, Cancer Institute, University College London, London, United Kingdom., Pezić D; Research Department of Cancer Biology, Cancer Institute, University College London, London, United Kingdom., Bhamra A; Proteomics Research Translational Technology Platform, Cancer Institute, University College London, London, United Kingdom., Surinova S; Proteomics Research Translational Technology Platform, Cancer Institute, University College London, London, United Kingdom., Jenner RG; Regulatory Genomics Group, Cancer Institute, University College London, London, United Kingdom., Cosma MP; Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Barcelona, Spain.; Universitat Pompeu Fabra (UPF), Barcelona, Spain.; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain., Hadjur S; Research Department of Cancer Biology, Cancer Institute, University College London, London, United Kingdom.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2023 Apr 03; Vol. 12. Date of Electronic Publication: 2023 Apr 03.
DOI:	10.7554/eLife.79386
Abstrakt:	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. Competing Interests: HP, YL, MN, MB, WV, LM, MC, DP, AB, SS, RJ, MC, SH No competing interests declared (© 2023, Porter, Li et al.)
Databáze:	MEDLINE
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