Published 17 March 2003. doi:10.1083/jcb.200212128
© The Rockefeller University Press,
0021-9525/2003/3/823 $5.00
The Journal of Cell Biology, Volume 160, Number 6, 823-831
The RasGAP-associated endoribonuclease G3BP assembles stress granules
Hélène Tourrière,
Karim Chebli,
Latifa Zekri,
Brice Courselaud,
Jean Marie Blanchard,
Edouard Bertrand and
Jamal Tazi
Institut de Génétique Moléculaire de Montpellier, UMR 5535 du Centre National de la Recherche Scientifique (CNRS), Université Montpellier II, 34293 Montpellier, Cedex 5, France
Address correspondence to Jamal Tazi, Institut de Génétique Moléculaire de Montpellier, UMR 5535 du CNRS, IFR 122, 1919 Route de Mende, 34293 Montpellier, Cedex 5, France. Tel.: 33 (0) 4-67-61-36-85. Fax: 33 (0) 4-67-04-02-31. E-mail: tazi{at}igm.cnrs-mop.fr
Stress granules (SGs) are formed in the cytoplasm in response to various toxic agents, and are believed to play a critical role in the regulation of mRNA metabolism during stress. In SGs, mRNAs are stored in an abortive translation initiation complex that can be routed to either translation initiation or degradation. Here, we show that G3BP, a phosphorylation-dependent endoribonuclease that interacts with RasGAP, is recruited to SGs in cells exposed to arsenite. G3BP may thus determine the fate of mRNAs during cellular stress. Remarkably, SG assembly can be either dominantly induced by G3BP overexpression, or on the contrary, inhibited by expressing a central domain of G3BP. This region binds RasGAP and contains serine 149, whose dephosphorylation is induced by arsenite treatment. Critically, a phosphomimetic mutant (S149E) fails to oligomerize and to assemble SGs, whereas a nonphosphorylatable G3BP mutant (S149A) does both. These results suggest that G3BP is an effector of SG assembly, and that Ras signaling contributes to this process by regulating G3BP dephosphorylation.
Key Words: mRNA stability; protein phosphorylation; mammalian endoribonucleases; Ras signaling; RNA-binding protein
H. Tourrière and K. Chebli contributed equally to this paper.
* Abbreviations used in this paper: RRM, RNA recognition motif; Ser 149, serine 149; SG, stress granule.

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