The RasGAP-associated endoribonuclease G3BP assembles stress granules

H. Tourriere (1) , K. Chebli (2) , L. Zekri , B. Courselaud , J. M. Blanchard (2) , Edouard Bertrand (2) , J. Tazi (2)

1 IGH - Institut de génétique humaine
2 IGMM - Institut de Génétique Moléculaire de Montpellier

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.

Mots clés: Amino Acid Sequence/physiology Animals Arsenates/pharmacology COS Cells Carrier Proteins/genetics/*metabolism Cell Hypoxia/drug effects/physiology Cytoplasmic Granules/*enzymology/genetics Endoribonucleases/genetics/*metabolism Eukaryotic Cells/*enzymology Gene Expression Regulation; Enzymologic/drug effects/physiology Hela Cells Humans Mutation/physiology Phosphorylation/drug effects Protein Structure; Messenger/*metabolism Serine/metabolism Stress/*enzymology/genetics ras GTPase-Activating Proteins/genetics/*metabolism; Tertiary/drug effects/physiology RNA

Domaines: Biochimie, Biologie Moléculaire

H. Tourriere, K. Chebli, L. Zekri, B. Courselaud, J. M. Blanchard, et al.. The RasGAP-associated endoribonuclease G3BP assembles stress granules. Journal of Cell Biology, 2003, 160 (6), pp.823--31. ⟨10.1083/jcb.200212128⟩. ⟨hal-02199834⟩