C/EBPβΔuORF mice—a genetic model for uORF-mediated translational control in mammals

C/EBPβΔuORF mice—a genetic model for uORF-mediated translational control in mammals

Upstream ORFs (uORFs) are translational control elements found predominantly in transcripts of key regulatory genes. No mammalian genetic model exists to experimentally validate the physiological relevance of uORF-regulated translation initiation. We report that mice deficient for the CCAAT/enhancer...

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Veröffentlicht in:Genes & development 2010-01, Vol.24 (1), p.15-20
Hauptverfasser: Wethmar, Klaus, Bégay, Valérie, Smink, Jeske J., Zaragoza, Katrin, Wiesenthal, Volker, Dörken, Bernd, Calkhoven, Cornelis F., Leutz, Achim
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Research Communication
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container_issue 1
container_start_page 15
container_title Genes & development
container_volume 24
creator Wethmar, Klaus
Bégay, Valérie
Smink, Jeske J.
Zaragoza, Katrin
Wiesenthal, Volker
Dörken, Bernd
Calkhoven, Cornelis F.
Leutz, Achim
description Upstream ORFs (uORFs) are translational control elements found predominantly in transcripts of key regulatory genes. No mammalian genetic model exists to experimentally validate the physiological relevance of uORF-regulated translation initiation. We report that mice deficient for the CCAAT/enhancer-binding protein β (C/EBPβ) uORF initiation codon fail to initiate translation of the autoantagonistic LIP (liver inhibitory protein) C/EBPβ isoform. C/EBPβ ΔuORF mice show hyperactivation of acute-phase response genes, persistent repression of E2F-regulated genes, delayed and blunted S-phase entry of hepatocytes after partial hepatectomy, and impaired osteoclast differentiation. These data and the widespread prevalence of uORFs in mammalian transcriptomes suggest a comprehensive role of uORF-regulated translation in (patho)physiology.
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title C/EBPβΔuORF mice—a genetic model for uORF-mediated translational control in mammals
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