RNA-binding proteins TIA-1 and TIAR link the phosphorylation of eIF-2 alpha to the assembly of mammalian stress granules

Citation
Nl. Kedersha et al., RNA-binding proteins TIA-1 and TIAR link the phosphorylation of eIF-2 alpha to the assembly of mammalian stress granules, J CELL BIOL, 147(7), 1999, pp. 1431-1441
Citations number
49
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
JOURNAL OF CELL BIOLOGY
ISSN journal
0021-9525 → ACNP
Volume
147
Issue
7
Year of publication
1999
Pages
1431 - 1441
Database
ISI
SICI code
0021-9525(199912)147:7<1431:RPTATL>2.0.ZU;2-U
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 pl ant cells (Nover et al., 1989; Never et al., 1983; Scharf et al,, 1998). Th e accumulation of untranslated mRNA at SGs is reversible in cells that reco ver from a sublethal stress, but irreversible in cells subjected to a letha l stress. We have found that the assembly of TIA-1/R+ SGs is initiated by t he phosphorylation of eIF-2 alpha. A phosphomimetic eIF-2 alpha mutant (S51 D) induces the assembly of SGs, whereas a nonphosphorylatable eIF-2 alpha m utant (S51A) prevents the assembly of SGs. The ability of a TIA-1 mutant la cking its RNA-binding domains to function as a transdominant inhibitor of S G formation suggests that this RNA-binding protein acts downstream of the p hosphorylation of eIF-2 alpha to promote the sequestration of untranslated mRNAs at SGs. The assembly and disassembly of SGs could regulate the durati on of stress-induced translational arrest in cells recovering from environm ental stress.