Inhibition of Ribosome Recruitment Induces Stress Granule Formation Independently of Eukaryotic Initiation Factor 2α Phosphorylation

• DOI: 10.1091/mbc.e06-04-0318
• Publication Date: 2006-07-27T00:40:26Z
• Authors: Rachid Mazroui; Rami Sukarieh; Marie-Eve Bordeleau; Randal J. Kaufman; Peter Northcote; Junichi Tanaka; Imed Gallouzi; Jerry Pelletier
• Keywords: 0303 health sciences; Models, Genetic; Eukaryotic Initiation Factor-2; DNA Helicases; RNA-Binding Proteins; Cytoplasmic Granules; ELAV-Like Protein 1; Poliovirus; 03 medical and health sciences; RNA Recognition Motif Proteins; ELAV Proteins; Peptide Initiation Factors; Protein Biosynthesis; Antigens, Surface; Eukaryotic Initiation Factor-4A; Humans; Phosphorylation; RNA, Small Interfering; Carrier Proteins; Poly-ADP-Ribose Binding Proteins; RNA Helicases; HeLa Cells

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)2α 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 eIF2α phosphorylation. We also show that inhibition of eIF4A activity does not impair the ability of eIF2α 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 eIF2α phosphorylation-dependent and -independent pathways that target translation initiation.