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Molecular and Cellular Biology, November 2001, p. 7747-7760, Vol. 21, No. 22
Institut de Génétique
Moléculaire de Montpellier (IGM), UMR 5535 CNRS, Université
Montpellier II, IFR 24, F34293 Montpellier Cedex
5,1 and Centre de Recherche de Biochimie
Macromoléculaire, UPR 1086, IFR 24, F34293 Montpellier, Cedex
1,3 France; Howard Hughes Medical
Institute, Yale University School of Medicine, New Haven,
Connecticut 06536-08122; and University
of California, San Diego, Department of Chemistry and Biochemistry,
La Jolla, California 92093-03594
Received 21 June 2001/Returned for modification 17 July
2001/Accepted 23 August 2001
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.
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.22.7747-7760.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
RasGAP-Associated Endoribonuclease G3BP: Selective RNA
Degradation and Phosphorylation-Dependent Localization
*
Corresponding author. Mailing address: Inst. de Gen.
Mol. de Mont. (IGM), UMR 5535 CNRS, Université Montpellier II,
CNRS, IFR 24, F34293 Montpellier Cedex 5, France. Phone: 33 (0) 4 67 61 36 85. Fax: 33 (0) 4 67 04 02 45. E-mail:
tazi{at}igm.cnrs-mop.fr.
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