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Published online 11 December 2000. doi:10.1083/jcb.151.6.1257
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© The Rockefeller University Press, 0021-9525/2000//1257 $5.00
The Journal of Cell Biology, Volume 151, Number 6, , 2000 1257-1268

Original Article

Dynamic Shuttling of Tia-1 Accompanies the Recruitment of mRNA to Mammalian Stress Granules



Nancy Kedershaa, Michael R. Chob, Wei Lia, Patrick W. Yaconob, Samantha Chena, Natalie Gilksa, David E. Golanb, and Paul Andersona

a Division of Rheumatology and Immunology, Harvard Medical School, Hematology Division, Brigham and Women's Hospital, Boston, Massachusetts 02115
b Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Hematology Division, Brigham and Women's Hospital, Boston, Massachusetts 02115
Division of Rheumatology and Immunology, Brigham and Women's Hospital, Smith 652, One Jimmy Fund Way, Boston, MA 02115.(617) 525-1310(617) 525-1202

panderson{at}rics.bwh.harvard.edu

Mammalian stress granules (SGs) harbor untranslated mRNAs that accumulate in cells exposed to environmental stress. Drugs that stabilize polysomes (emetine) inhibit the assembly of SGs, whereas drugs that destabilize polysomes (puromycin) promote the assembly of SGs. Moreover, emetine dissolves preformed SGs as it promotes the assembly of polysomes, suggesting that these mRNP species (i.e., SGs and polysomes) exist in equilibrium. We used green flourescent protein–tagged SG-associated RNA-binding proteins (specifically, TIA-1 and poly[A] binding protein [PABP-I]) to monitor SG assembly, disassembly, and turnover in live cells. Fluorescence recovery after photobleaching shows that both TIA-1 and PABP-I rapidly and continuously shuttle in and out of SGs, indicating that the assembly of SGs is a highly dynamic process. This unexpected result leads us to propose that mammalian SGs are sites at which untranslated mRNAs are sorted and processed for either reinitiation, degradation, or packaging into stable nonpolysomal mRNP complexes. A truncation mutant of TIA-1 (TIA-1{Delta}RRM), which acts as a transdominant inhibitor of SG assembly, promotes the expression of cotransfected reporter genes in COS transfectants, suggesting that this process of mRNA triage might, directly or indirectly, influence protein expression.

Key Words: TIA-1 • stress granules • protein translation • eIF-2{alpha} • PABP-1

© 2000 The Rockefeller University Press

The online version of this article contains supplemental material.

Abbreviations used in this paper: ARE, AU-rich element; eIF, eukaryotic initiation factor; HA, hemagglutinin; PABP-I, poly(A)+ binding protein I; PrD, prion-related domain; RRM, RNA recognition motif; SG, stress granule.


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