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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3' Untranslated Regions / metabolism
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Amino Acid Substitution
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Animals
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Base Sequence
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Binding Sites
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Nucleus / metabolism
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Cells, Cultured
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Cytoplasm / metabolism
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DNA Helicases
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Endoribonucleases / genetics
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Endoribonucleases / metabolism*
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Fibroblasts / cytology
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Glutamic Acid / genetics
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Glutamic Acid / metabolism
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Isoenzymes / genetics
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Isoenzymes / metabolism
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Mice
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Mice, Knockout
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Phosphorylation
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Poly-ADP-Ribose Binding Proteins
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Proto-Oncogene Proteins c-myc / genetics*
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RNA Helicases
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RNA Recognition Motif Proteins
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RNA, Messenger / metabolism*
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Serine / genetics
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Serine / metabolism
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Substrate Specificity
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p120 GTPase Activating Protein / genetics
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p120 GTPase Activating Protein / metabolism*
Substances
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3' Untranslated Regions
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Carrier Proteins
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Isoenzymes
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Poly-ADP-Ribose Binding Proteins
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Proto-Oncogene Proteins c-myc
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RNA Recognition Motif Proteins
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RNA, Messenger
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p120 GTPase Activating Protein
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Glutamic Acid
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Serine
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Endoribonucleases
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DNA Helicases
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G3bp1 protein, mouse
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RNA Helicases