Abstract
In response to environmental stress, the related RNA-binding proteins TIA-1 and TIAR colocalize with poly(A)+ RNA at cytoplasmic foci that resemble the stress granules (SGs) that harbor untranslated mRNAs in heat shocked plant cells (Nover et al. 1989; Nover et al. 1983; Scharf et al. 1998). The accumulation of untranslated mRNA at SGs is reversible in cells that recover from a sublethal stress, but irreversible in cells subjected to a lethal stress. We have found that the assembly of TIA-1/R+ SGs is initiated by the phosphorylation of eIF-2α. A phosphomimetic eIF-2α mutant (S51D) induces the assembly of SGs, whereas a nonphosphorylatable eIF-2α mutant (S51A) prevents the assembly of SGs. The ability of a TIA-1 mutant lacking its RNA-binding domains to function as a transdominant inhibitor of SG formation suggests that this RNA-binding protein acts downstream of the phosphorylation of eIF-2α to promote the sequestration of untranslated mRNAs at SGs. The assembly and disassembly of SGs could regulate the duration of stress- induced translational arrest in cells recovering from environmental stress.
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Dates
Type | When |
---|---|
Created | 23 years, 1 month ago (July 26, 2002, 12:45 p.m.) |
Deposited | 2 years, 1 month ago (July 28, 2023, 9:53 p.m.) |
Indexed | 57 minutes ago (Sept. 3, 2025, 6:01 a.m.) |
Issued | 25 years, 8 months ago (Dec. 27, 1999) |
Published | 25 years, 8 months ago (Dec. 27, 1999) |
Published Online | 25 years, 8 months ago (Dec. 27, 1999) |
Published Print | 25 years, 8 months ago (Dec. 27, 1999) |
@article{Kedersha_1999, title={RNA-Binding Proteins Tia-1 and Tiar Link the Phosphorylation of Eif-2α to the Assembly of Mammalian Stress Granules}, volume={147}, ISSN={1540-8140}, url={http://dx.doi.org/10.1083/jcb.147.7.1431}, DOI={10.1083/jcb.147.7.1431}, number={7}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Kedersha, Nancy L. and Gupta, Mita and Li, Wei and Miller, Ira and Anderson, Paul}, year={1999}, month=dec, pages={1431–1442} }