RT Journal Article
SR Electronic
T1 Cohesin-independent STAG proteins interact with RNA and localise to R-loops to promote complex loading
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.02.20.432055
DO 10.1101/2021.02.20.432055
A1 Hayley Porter
A1 Yang Li
A1 Maria Victoria Neguembor
A1 Manuel Beltran
A1 Wazeer Varsally
A1 Laura Martin
A1 Manuel Tavares Cornejo
A1 Dubravka Pezic
A1 Amandeep Bhamra
A1 Silvia Surinova
A1 Richard G. Jenner
A1 Maria Pia Cosma
A1 Suzana Hadjur
YR 2023
UL http://biorxiv.org/content/early/2023/01/24/2021.02.20.432055.abstract
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 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.Competing Interest StatementThe authors have declared no competing interest.