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Cited by 622

The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.

Evidence That Ternary Complex (eIF2-GTP-tRNAiMet)–Deficient Preinitiation Complexes Are Core Constituents of Mammalian Stress Granules

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Kedersha, Nancy, Chen, Samantha, Gilks, Natalie, Li, Wei, Miller, Ira J., Stahl, Joachim, Anderson, Paul·2002·Molecular Biology of the Cell

Abstract

Environmental stress-induced phosphorylation of eIF2α 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 eIF2α 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-eIF2α 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.

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Metadata

Authors
Kedersha, N., Chen, S., Gilks, N., Li, W., Miller, I. J., Stahl, J., & Anderson, P.
Venue
Molecular Biology of the Cell
Published
2002-01
Volume
13
Issue
1
Pages
195-210
ISSN
  • 1059-1524 (ISSN-L)
  • 1939-4586
OpenAlex
W2049311171
Cited by
622
References
25
FWCI
4.64
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Evidence That Ternary Complex (eIF2-GTP-tRNAiMet)–Deficient Preinitiation Complexes Are Core Constituents of Mammalian Stress Granules. https://app.cochat.ai/papers/10.1091/mbc.01-05-0221
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Kedersha, N., Chen, S., Gilks, N., Li, W., Miller, I. J., Stahl, J., & Anderson, P. (2002). Evidence That Ternary Complex (eIF2-GTP-tRNAiMet)–Deficient Preinitiation Complexes Are Core Constituents of Mammalian Stress Granules. Molecular Biology of the Cell. https://doi.org/10.1091/mbc.01-05-0221

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