title: Stress-specific differences in assembly and composition of stress granules and related foci.
abstract: Cells have developed different mechanisms to respond to stress, including the formation of cytoplasmic foci known as stress granules (SGs). SGs are dynamic and formed as a result of stress-induced inhibition of translation. Despite enormous interest in SGs due to their contribution to the pathogenesis of several human diseases, many aspects of SG formation are poorly understood. SGs induced by different stresses are generally assumed to be uniform, although some studies suggest that different SG subtypes and SG-like cytoplasmic foci exist. Here, we investigated the molecular mechanisms of SG assembly and characterized their composition when induced by various stresses. Our data revealed stress-specific differences in composition, assembly and dynamics of SGs and SG-like cytoplasmic foci. Using a set of genetically modified haploid human cells, we determined the molecular circuitry of stress-specific translation inhibition upstream of SG formation and its relation to cell survival. Finally, our studies characterize cytoplasmic stress-induced foci related to, but distinct from, canonical SGs, and also introduce haploid cells as a valuable resource to study RNA granules and translation control mechanisms.
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA.|Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Anaïs
authors.initials: A
authors.lastname: Aulas
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA.|Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Marta M
authors.initials: MM
authors.lastname: Fay
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA.|Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Shawn M
authors.initials: SM
authors.lastname: Lyons
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA.|Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Achorn
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA.|Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Kedersha
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA.|Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Anderson
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA pivanov@rics.bwh.harvard.edu.|Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.|The Broad Institute of Harvard and M.I.T., Cambridge, MA 02142, USA.
authors.forename: Pavel
authors.identifier: 0000-0002-7986-7760
authors.initials: P
authors.lastname: Ivanov
mesh_terms: D000818:Animals; D018053:Arsenites / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism*; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D055786:Gene Knockout Techniques; D006801:Humans; D051379:Mice; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017670:Sodium Compounds / Q000494:pharmacology; D013312:Stress, Physiological / Q000187:drug effects
chemical_list: D018053:Arsenites; D015852:Eukaryotic Initiation Factor-2; D017670:Sodium Compounds; C017947:sodium arsenite; D017346:Protein Serine-Threonine Kinases
keywords: Haploid cell; Stress granules; Stress response; Translation initiation; Translational control; eIF2α