Translation control of UCP2 synthesis by the upstream open reading frame |
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Authors: | C Hurtaud C Gelly F Bouillaud C Lévi-Meyrueis |
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Institution: | (1) BIOTRAM, CNRS UPR9078, Faculté de Médecine Necker Enfants Malades, Université René Descartes, 156 rue de Vaugirard, 75730 Paris, France |
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Abstract: | 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.
Received 22 March 2006; received after revision 19 May 2006; accepted 8 June 2006
C. Hurtaud and C. Gelly contributed equally to this work. |
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Keywords: | UCP2 mitochondria translation 5′ untranslated region uORF |
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