Mammalian Staufen 1 is recruited to stress granules and impairs their assembly

• Autores: Thomas, M.G.; Martinez Tosar, L.J.; Desbats, M.A.; Leishman, C.C.; Boccaccio, G.L.
• Año de publicación: 2009
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: J. Cell Sci. 2009;122(4):563-573
• Materia: ER stress; Oxidative stress; P bodies; Silencing foci; Staufen; Stress granules; initiation factor 2alpha; RNA binding protein; staufen 1; unclassified drug; enzyme inhibitor; heat shock protein 70; initiation factor 2; RNA binding protein; small interfering RNA; staufen protein, mammalian; thapsigargin; animal cell; article; cell granule; cellular stress response; controlled study; endoplasmic reticulum stress; gene overexpression; gene silencing; human; human cell; nonhuman; oxidative stress; polysome; priority journal; protein assembly; protein phosphorylation; regulatory mechanism; translation initiation; animal; biosynthesis; cell granule; cell strain 3T3; cell strain COS1; Cercopithecus; chemistry; confocal microscopy; drug effect; endoplasmic reticulum; HeLa cell; metabolism; mouse; physiological stress; physiology; protein synthesis; protein tertiary structure; rat; ultrastructure; Mammalia; Animals; Cercopithecus aethiops; COS Cells; Cytoplasmic Granules; Endoplasmic Reticulum; Enzyme Inhibitors; Eukaryotic Initiation Factor-2; Hela Cells; HSP70 Heat-Shock Proteins; Humans; Mice; Microscopy, Confocal; NIH 3T3 Cells; Oxidative Stress; Polyribosomes; Protein Biosynthesis; Protein Structure, Tertiary; Rats; RNA, Small Interfering; RNA-Binding Proteins; Stress, Physiological; Thapsigargin
• Institución: Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales

Stress granules are cytoplasmic mRNA-silencing foci that form transiently during the stress response. Stress granules harbor abortive translation initiation complexes and are in dynamic equilibrium with translating polysomes. Mammalian Staufen 1 (Stau1) is a ubiquitous double-stranded RNA-binding protein associated with polysomes. Here, we show that Stau1 is recruited to stress granules upon induction of endoplasmic reticulum or oxidative stress as well in stress granules induced by translation initiation blockers. We found that stress granules lacking Stau1 formed in cells depleted of this molecule, indicating that Stau1 is not an essential component of stress granules. Moreover, Stau1 knockdown facilitated stress granule formation upon stress induction. Conversely, transient transfection of Stau1 impaired stress granule formation upon stress or pharmacological initiation arrest. The inhibitory capacity of Stau1 mapped to the amino-terminal half of the molecule, a region known to bind to polysomes. We found that the fraction of polysomes remaining upon stress induction was enriched in Stau1, and that Stau1 overexpression stabilized polysomes against stress. We propose that Stau1 is involved in recovery from stress by stabilizing polysomes, thus helping stress granule dissolution.
Fil:Thomas, M.G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Martinez Tosar, L.J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Desbats, M.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Boccaccio, G.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.