Metazoan stress granule assembly is mediated by P-eIF2α-dependent and -independent mechanisms
- 1Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
- 2Department of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA
Abstract
Stress granules (SGs) are cytoplasmic bodies wherein translationally silenced mRNAs are recruited for triage in response to environmental stress. We report that Drosophila cells form SGs in response to arsenite and heat shock. Drosophila SGs, like mammalian SGs, are distinct from but adjacent to processing bodies (PBs, sites of mRNA silencing and decay), require polysome disassembly, and are in dynamic equilibrium with polysomes. We further examine the role of the two Drosophila eIF2α kinases, PEK and GCN2, in regulating SG formation in response to heat and arsenite stress. While arsenite-induced SGs are dependent upon eIF2α phosphorylation, primarily via PEK, heat-induced SGs are phospho-eIF2α-independent. In contrast, heat-induced SGs require eIF2α phosphorylation in mammalian cells, as non-phosphorylatable eIF2α Ser51Ala mutant murine embryonic fibroblasts do not form SGs even after severe heat shock. These results suggest that mammals evolved alternative mechanisms for dealing with thermal stress.
Keywords
Footnotes
-
Reprint requests to: Pamela A. Silver, Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA; e-mail: pamela_silver{at}hms.harvard.edu; fax: (617) 432-5012.
-
Abbreviations: SG, stress granule; PB, processing body; GFP, green fluorescent protein; eIF, eukaryotic initiation factor; PEK/PERK, pancreatic eIF2α kinase/PKR-like ER-localized eIF2α kinase; GCN2, general control nonderepressing 2 kinase; MEF, mouse embryonic fibroblast.
-
Article published online ahead of print. Article and publication date are at http://www.rnajournal.org/cgi/doi/10.1261/rna.1684009.
-
- Received April 9, 2009.
- Accepted June 30, 2009.
- Copyright © 2009 RNA Society
