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© The Rockefeller University Press, 0021-9525/1999//1431 $5.00
The Journal of Cell Biology, Volume 147, Number 7, , 1999 1431-1442

Original Article

RNA-Binding Proteins Tia-1 and Tiar Link the Phosphorylation of Eif-2{alpha} to the Assembly of Mammalian Stress Granules



Nancy L. Kedershaa, Mita Guptaa, Wei Lia, Ira Millera, and Paul Andersona

a Division of Rheumatology and Immunology, Brigham and Women's Hospital, Smith Building, Boston, Massachusetts 02115
Division of Rheumatology and Immunology, Brigham and Women's Hospital, Smith 652, 75 Francis Street, Boston, MA 02115.(617) 525-1310(617) 525-1202

panderson{at}rics.bwh.harvard.edu

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-2{alpha}. A phosphomimetic eIF-2{alpha} mutant (S51D) induces the assembly of SGs, whereas a nonphosphorylatable eIF-2{alpha} 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-2{alpha} 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.

Key Words: RNA-binding proteins • stress • translational control • eIF-2{alpha}

© 1999 The Rockefeller University Press

Abbreviations used in this paper: HA, hemagglutinin; HSG, heat shock granule; HSP, heat shock protein; PABP-I, poly (A)+ binding protein I; RNP, ribonuclear protein, SG, stress granule.


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