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| Item Type: | Article |
|---|---|
| Title: | Evidence that ternary complex (eIF2-GTP-tRNAiMet)-deficient preinitiation complexes are core constituents of mammalian stress granules |
| Creators Name: | Kedersha, N., Chen, S., Gilks, N., Li, W., Miller, I.J., Stahl, J. and Anderson, P. |
| Abstract: | Environmental stress-induced phosphorylation of eIF2alpha inhibits protein translation by reducing the availability of eIF2-GTP-tRNA(i)Met, the ternary complex that joins initiator tRNA(Met) to the 43S preinitiation complex. The resulting untranslated mRNA is dynamically routed to discrete cytoplasmic foci known as stress granules (SGs), a process requiring the related RNA-binding proteins TIA-1 and TIAR. SGs appear to be in equilibrium with polysomes, but the nature of this relationship is obscure. We now show that most components of the 48S preinitiation complex (i.e., small, but not large, ribosomal subunits, eIF3, eIF4E, eIF4G) are coordinately recruited to SGs in arsenite-stressed cells. In contrast, eIF2 is not a component of newly assembled SGs. Cells expressing a phosphomimetic mutant (S51D) of eIF2alpha assemble SGs of similar composition, confirming that the recruitment of these factors is a direct consequence of blocked translational initiation and not due to other effects of arsenite. Surprisingly, phospho-eIF2alpha is recruited to SGs that are disassembling in cells recovering from arsenite-induced stress. We discuss these results in the context of a translational checkpoint model wherein TIA and eIF2 are functional antagonists of translational initiation, and in which lack of ternary complex drives SG assembly. |
| Keywords: | Arsenites, COS Cells, Density Gradient Centrifugation, Cercopithecus Aethiops, Cytoplasmic Granules, Eukaryotic Initiation Factor-2, Guanosine Triphosphate, Macromolecular Substances, Fluorescence Microscopy, Translational Peptide Chain Initiation, Peptide Initiation Factors, Phosphorylation, Messenger RNA, Ribosomal RNA, Met Transfer RNA, RNA-Binding Proteins, Transfection, Cultured Tumor Cells, Animals |
| Source: | Molecular Biology of the Cell |
| ISSN: | 1059-1524 |
| Publisher: | American Society for Cell Biology |
| Volume: | 13 |
| Number: | 1 |
| Page Range: | 195-210 |
| Date: | January 2002 |
| Additional Information: | Copyright (c) 2002 by The American Society for Cell Biology |
| Official Publication: | https://doi.org/10.1091/mbc.01-05-0221 |
| PubMed: | View item in PubMed |
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