RasGAP-associated endoribonuclease G3Bp: selective RNA degradation and phosphorylation-dependent localization

Tourriere, H.; Gallouzi, I. E.; Chebli, K.; Capony, J. P.; Mouaikel, J.; van der Geer, P.; Tazi, J.

Mol Cell Biol

2001-11 / vol 21 / pages 7747-60


Mitogen activation of mRNA decay pathways likely involves specific endoribonucleases, such as G3BP, a phosphorylation-dependent endoribonuclease that associates with RasGAP in dividing but not quiescent cells. G3BP exclusively cleaves between cytosine and adenine (CA) after a specific interaction with RNA through the carboxyl-terminal RRM-type RNA binding motif. Accordingly, G3BP is tightly associated with a subset of poly(A)(+) mRNAs containing its high-affinity binding sequence, such as the c-myc mRNA in mouse embryonic fibroblasts. Interestingly, c-myc mRNA decay is delayed in RasGAP-deficient fibroblasts, which contain a defective isoform of G3BP that is not phosphorylated at serine 149. A G3BP mutant in which this serine is changed to alanine remains exclusively cytoplasmic, whereas a glutamate for serine substitution that mimics the charge of a phosphorylated serine is translocated to the nucleus. Thus, a growth factor-induced change in mRNA decay may be modulated by the nuclear localization of a site-specific endoribonuclease such as G3BP.

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Animals; Cells, Cultured; Mice; Mice, Knockout; Molecular Sequence Data; Phosphorylation; Base Sequence; Cell Nucleus/metabolism; Binding Sites; Substrate Specificity; Amino Acid Substitution; Mutagenesis, Site-Directed; Cytoplasm/metabolism; Proto-Oncogene Proteins c-myc/*genetics; 3' Untranslated Regions/metabolism; Carrier Proteins/genetics/*metabolism; Endoribonucleases/genetics/*metabolism; Fibroblasts/cytology; Glutamic Acid/genetics/metabolism; Isoenzymes/genetics/metabolism; p120 GTPase Activating Protein/genetics/*metabolism; RNA, Messenger/*metabolism; Serine/genetics/metabolism

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