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

H. Tourrière, I. E. Gallouzi, K. Chebli, J. P. Capony, J. Mouaikel, P. Van der Geer, J. Tazi

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145 Scopus citations

Abstract

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.
Original languageEnglish (US)
Pages (from-to)7747-7760
Number of pages14
JournalMolecular and Cellular Biology
Volume21
Issue number22
DOIs
StatePublished - Nov 1 2001
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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