Mammalian Staufen 1 is recruited to stress granules and impairs their assembly.
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.
Thomas
María Gabriela
MG
Fundación Instituto Leloir, Av. Patricias Argentinas 435, Buenos Aires, Argentina.
Martinez Tosar
Leandro J
LJ
Desbats
María Andrea
MA
Leishman
Claudia C
CC
Boccaccio
Graciela L
GL
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003594:Cytoplasmic Granules / Q000378:metabolism* / Q000648:ultrastructure; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal; D041681:NIH 3T3 Cells; D018384:Oxidative Stress / Q000502:physiology; D011132:Polyribosomes / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D017434:Protein Structure, Tertiary / Q000502:physiology; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D051381:Rats; D013312:Stress, Physiological; D019284:Thapsigargin / Q000494:pharmacology
D004791:Enzyme Inhibitors; D015852:Eukaryotic Initiation Factor-2; D018840:HSP70 Heat-Shock Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C117884:staufen protein, mammalian; D019284:Thapsigargin