Cohesin-independent STAG proteins interact with RNA and R-loops and promote complex loading
- University College London, United Kingdom
- Barcelona Institute of Science and Technology, Spain
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, RNA binding proteins 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.
Data availability
All data has been made freely available. Please see Page 21 of the manuscript for Accession numbers.
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ChIP-seq dataNCBI Gene Expression Omnibus, GSE167887.
Article and author information
Author details
Maria Victoria Neguembor
Funding
Wellcome Trust (106985/Z/15/Z)
- Suzana Hadjur
Cancer Research UK (PhD studentship)
- Hayley Porter
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Andrés Aguilera, CABIMER, Universidad de Sevilla, Spain
Version history
- Preprint posted: February 20, 2021 (view preprint)
- Received: April 10, 2022
- Accepted: April 2, 2023
- Accepted Manuscript published: April 3, 2023 (version 1)
- Version of Record published: June 2, 2023 (version 2)
Copyright
© 2023, Porter et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Cohesin-independent STAG proteins interact with RNA and R-loops and promote complex loading
eLife 12:e79386.
https://doi.org/10.7554/eLife.79386
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