RasGAP-associated endoribonuclease G3BP: Selective RNA degradation and phosphorylation-dependent localization

Mitogen activation of mRNA decay pathways likely involves specific endoribo nucleases, such as G3BP, a phosphorylation-dependent endoribonuclease that associates with RasGAP in dividing but not quiescent cells. G3BP exclusivel y cleaves between cytosine and adenine (CA) after a specific interaction wi th RNA through the carboxyl-terminal RRM-type RNA binding motif. Accordingl y, 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 embryon ic fibroblasts. Interestingly, c-myc mRNA decay is delayed in RasGAP-defici ent fibroblasts, which contain a defective isoform of G3BP that is not phos phorylated at serine 149. A G3BP mutant in which this serine. is changed to alanine remains exclusively cytoplasmic, whereas a glutamate for serine su bstitution that mimics the charge of a phosphorylated serine is translocate d 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.