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Vol. 17, Issue 10, 4212-4219, October 2006
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Phosphorylation
,
*Department of Biochemistry and @McGill Cancer Center, McIntyre Medical Sciences Building, McGill University, Montreal, Quebec, Canada H3G 1Y6; Howard Hughes Medical Institute and Departments of Biological Chemistry and Internal Medicine, University of Michigan, Ann Arbor, MI 48109; ||School of Chemical and Physical Sciences, Victoria University of Wellington, Wellington 6140, New Zealand; and ¶Department of Chemistry, Biology, and Marine Sciences, University of the Ryukyus, Nishihara, Okinawa 903-0213, Japan
Submitted April 18, 2006;
Revised July 13, 2006;
Accepted July 17, 2006
Monitoring Editor: Peter Walter
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)2
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 eIF2 phosphorylation. We also show that inhibition of eIF4A activity does not impair the ability of eIF2 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 eIF2 phosphorylation-dependent and -independent pathways that target translation initiation.
The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org). This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E06-04-0318) on July 26, 2006.
These authors contributed equally to this work.
# These authors contributed equally to this work.
Address correspondence to: Jerry Pelletier (jerry.pelletier{at}mcgill.ca)
Abbreviations used: AS, arsenite; eIF, eukaryotic initiation factor; MEF, mouse embryo fibroblast; PABP, poly(A) binding protein; PB, processing body; PI, postinfection; SG, stress granule; siRNA, short interfering RNA; uORF, upstream open reading frame; UTR, untranslated region; wt, wild-type.
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