A Nuclear Stress Pathway that Parallels Cytoplasmic Stress Granule Formation
Tyler Quoc-Thai Do,
Antoine Gaudreau-Lapierre,
Carmen G. Palii,
Virginia Maria Ferreira Resende,
Denise Campuzano,
Claire Simada Aeschimann,
Majorie Brand,
Laura Trinkle-Mulcahy
Affiliations
Tyler Quoc-Thai Do
Department of Cellular and Molecular Medicine and Ottawa Institute of Systems Biology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Antoine Gaudreau-Lapierre
Department of Cellular and Molecular Medicine and Ottawa Institute of Systems Biology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Carmen G. Palii
Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8L6, Canada
Virginia Maria Ferreira Resende
Department of Cellular and Molecular Medicine and Ottawa Institute of Systems Biology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Denise Campuzano
Department of Cellular and Molecular Medicine and Ottawa Institute of Systems Biology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Claire Simada Aeschimann
Department of Cellular and Molecular Medicine and Ottawa Institute of Systems Biology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Majorie Brand
Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8L6, Canada
Laura Trinkle-Mulcahy
Department of Cellular and Molecular Medicine and Ottawa Institute of Systems Biology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada; Corresponding author
Summary: Stress adaptation is exploited by cancer cells to survive and proliferate under adverse conditions. Survival pathways induced by stress are thus highly promising therapeutic targets. One key pathway involves formation of cytoplasmic stress granules, which regulate the location, stability, and translation of specific mRNAs. Here, we describe a transcriptional stress response that is triggered by similar stressors and characterized by accumulation of RepoMan (cell division cycle associated 2) at nuclear stress foci (nucSF). Formation of these structures is reversible, and they are distinct from known nuclear organelles and stress bodies. Immunofluorescence analysis revealed accumulation of heterochromatic markers, and increased association of RepoMan with the adenylate cyclase 2 (ADCY2) gene locus in stressed cells accompanied reduced levels of ADCY2 mRNA and protein. Quantitative comparison of the RepoMan interactome in stressed vs. unstressed cells identified condensin II as a nucSF factor, suggesting their functional association in the establishment and/or maintenance of these facultative heterochromatic domains.
