RasGAP-associated endoribonuclease G3Bp: selective RNA degradation and phosphorylation-dependent localization.
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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Institut de Génétique Moléculaire de Montpellier (IGM), UMR 5535 CNRS, Université Montpellier II, IFR 24, F34293 Montpellier Cedex 5, France.
Gallouzi
I E
IE
Chebli
K
K
Capony
J P
JP
Mouaikel
J
J
van der Geer
P
P
Tazi
J
J
D020413:3' Untranslated Regions / Q000378:metabolism; D019943:Amino Acid Substitution; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004265:DNA Helicases; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology; D018698:Glutamic Acid / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D000075223:Poly-ADP-Ribose Binding Proteins; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D020365:RNA Helicases; D000067776:RNA Recognition Motif Proteins; D012333:RNA, Messenger / Q000378:metabolism*; D012694:Serine / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D020729:p120 GTPase Activating Protein / Q000235:genetics / Q000378:metabolism*
D020413:3' Untranslated Regions; D002352:Carrier Proteins; D007527:Isoenzymes; D000075223:Poly-ADP-Ribose Binding Proteins; D016271:Proto-Oncogene Proteins c-myc; D000067776:RNA Recognition Motif Proteins; D012333:RNA, Messenger; D020729:p120 GTPase Activating Protein; D018698:Glutamic Acid; D012694:Serine; D004722:Endoribonucleases; D004265:DNA Helicases; C492055:G3bp1 protein, mouse; D020365:RNA Helicases