title: Inhibition of ribosome recruitment induces stress granule formation independently of eukaryotic initiation factor 2alpha phosphorylation.
abstract: Cytoplasmic aggregates known as stress granules (SGs) arise as a consequence of cellular stress and contain stalled translation preinitiation complexes. These foci are thought to serve as sites of mRNA storage or triage during the cell stress response. SG formation has been shown to require induction of eukaryotic initiation factor (eIF)2alpha phosphorylation. Herein, we investigate the potential role of other initiation factors in this process and demonstrate that interfering with eIF4A activity, an RNA helicase required for the ribosome recruitment phase of translation initiation, induces SG formation and that this event is not dependent on eIF2alpha phosphorylation. We also show that inhibition of eIF4A activity does not impair the ability of eIF2alpha to be phosphorylated under stress conditions. Furthermore, we observed SG assembly upon inhibition of cap-dependent translation after poliovirus infection. We propose that SG modeling can occur via both eIF2alpha phosphorylation-dependent and -independent pathways that target translation initiation.
authors.affiliation: Department of Biochemistry, McGill University, Montreal, Quebec, Canada H3G 1Y6.
authors.forename: Rachid
authors.initials: R
authors.lastname: Mazroui
authors.forename: Rami
authors.initials: R
authors.lastname: Sukarieh
authors.forename: Marie-Eve
authors.initials: ME
authors.lastname: Bordeleau
authors.forename: Randal J
authors.initials: RJ
authors.lastname: Kaufman
authors.forename: Peter
authors.initials: P
authors.lastname: Northcote
authors.forename: Junichi
authors.initials: J
authors.lastname: Tanaka
authors.forename: Imed
authors.initials: I
authors.lastname: Gallouzi
authors.forename: Jerry
authors.initials: J
authors.lastname: Pelletier
mesh_terms: D000954:Antigens, Surface / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism*; D004265:DNA Helicases; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism* / Q000502:physiology; D039601:Eukaryotic Initiation Factor-4A / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008957:Models, Genetic; D010448:Peptide Initiation Factors / Q000378:metabolism*; D010766:Phosphorylation; D017955:Poliovirus / Q000235:genetics; D000075223:Poly-ADP-Ribose Binding Proteins; D014176:Protein Biosynthesis; D020365:RNA Helicases; D000067776:RNA Recognition Motif Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*
chemical_list: D000954:Antigens, Surface; D002352:Carrier Proteins; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D015852:Eukaryotic Initiation Factor-2; D010448:Peptide Initiation Factors; D000075223:Poly-ADP-Ribose Binding Proteins; D000067776:RNA Recognition Motif Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D039601:Eukaryotic Initiation Factor-4A; D004265:DNA Helicases; C116070:G3BP1 protein, human; D020365:RNA Helicases