Translation control of UCP2 synthesis by the upstream open reading frame.
Uncoupling protein 2 (UCP2) belongs to a family of transporters of the mitochondrial inner membrane. In vivo low expression of UCP2 contrasts with a high UCP2 mRNA level, and induction of UCP2 expression occurs without change in mRNA level, demonstrating a translational control. The UCP2 mRNA is characterized by a long 5' untranslated region (5'UTR), in which an upstream open reading frame (uORF) codes for a 36-amino-acid sequence. The 5'UTR and uORF have an inhibitory role in the translation of UCP2. The present study demonstrates that the 3' region of the uORF is a major determinant for this inhibitory role. In this 3' region, a single-base substitution that kept the codon sense unchanged significantly modified UCP2 translation, whereas some important amino acid changes had no effect. We discuss our results within the framework of the existing models explaining initiation of translation downstream of a uORF.
Hurtaud
C
C
BIOTRAM, CNRS UPR9078, Faculté de Médecine Necker Enfants Malades, Université René Descartes, 75730 Paris, France.
Gelly
C
C
Bouillaud
F
F
Lévi-Meyrueis
C
C
D020121:5' Untranslated Regions; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D007473:Ion Channels; D026901:Membrane Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D024101:Mitochondrial Proteins / Q000096:biosynthesis* / Q000235:genetics; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D016366:Open Reading Frames; D012333:RNA, Messenger / Q000096:biosynthesis*; D014158:Transcription, Genetic; D000071246:Uncoupling Protein 2
D020121:5' Untranslated Regions; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D000071246:Uncoupling Protein 2