c-Jun ARE targets mRNA deadenylation by an EDEN-BP (embryo deadenylation element-binding protein)-dependent pathway.
In mammalian cells, certain mRNAs encoding cytokines or proto-oncogenes are especially unstable, because of the presence of a particular sequence element in their 3'-untranslated region named ARE (A/U-rich element). AREs cause this instability by provoking the rapid shortening of the poly(A) tail of the mRNA. The deadenylation of mRNAs mediated by AREs containing repeats of the AUUUA motif (class I/II AREs) is conserved in Xenopus embryos. Here, we first extend these observations by showing that c-Jun ARE, a representative of class III (non-AUUUA) AREs, also provokes the deadenylation of a reporter RNA in Xenopus embryos. Next, by immunodepletion and immunoneutralization experiments, we show that, in Xenopus, the rapid deadenylation of RNAs that contain the c-Jun ARE, but not an AUUUA ARE, requires EDEN-BP. This RNA-binding protein was previously shown to provoke the rapid deadenylation of certain Xenopus maternal RNAs. Finally, we show that CUG-BP, the human homologue of EDEN-BP, specifically binds to c-Jun ARE. Together, these results identify CUG-BP as a plausible deadenylation factor responsible for the post-transcriptional control of c-Jun proto-oncogene mRNA in mammalian cells.
Paillard
Luc
L
CNRS UMR 6061, Université de Rennes 1, Faculté de Médecine, 2 Avenue Léon Bernard, 35043 Rennes Cedex, France. Luc.Paillard@univ-rennes1.fr
Legagneux
Vincent
V
Maniey
Dominique
D
Osborne
H Beverley
HB
D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D000067879:CELF1 Protein; D003001:Cloning, Molecular; D017931:DNA Primers; D004625:Embryo, Nonmammalian; D006801:Humans; D020319:Oligodeoxyribonucleotides, Antisense; D016366:Open Reading Frames; D000090063:Proto-Oncogene Mas; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics*; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015183:Restriction Mapping; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology
D020413:3' Untranslated Regions; D000067879:CELF1 Protein; C102843:CELF1 protein, human; D017931:DNA Primers; C110462:EDEN-specific RNA-binding protein, Xenopus; C000715470:MAS1 protein, human; D020319:Oligodeoxyribonucleotides, Antisense; D000090063:Proto-Oncogene Mas; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D029867:Xenopus Proteins