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Upstream open reading frames: molecular switches in (patho)physiology

Item Type:Review
Title:Upstream open reading frames: molecular switches in (patho)physiology
Creators Name:Wethmar, K. and Smink, J.J. and Leutz, A.
Abstract:Conserved upstream open reading frames (uORFs) are found within many eukaryotic transcripts and are known to regulate protein translation. Evidence from genetic and bioinformatic studies implicates disturbed uORF-mediated translational control in the etiology of human diseases. A genetic mouse model has recently provided proof-of-principle support for the physiological relevance of uORF-mediated translational control in mammals. The targeted disruption of the uORF initiation codon within the transcription factor CCAAT/enhancer binding protein beta (C/EBPbeta) gene resulted in deregulated C/EBPbeta protein isoform expression, associated with defective liver regeneration and impaired osteoclast differentiation. The high prevalence of uORFs in the human transcriptome suggests that intensified search for mutations within 5' RNA leader regions may reveal a multitude of alterations affecting uORFs, causing pathogenic deregulation of protein expression.
Keywords:C/EBP, Mutations, Translational Control, Tumorigenesis, uORF
Source:BioEssays
ISSN:0265-9247
Publisher:Wiley-Blackwell
Volume:32
Number:10
Page Range:885-893
Date:October 2010
Official Publication:https://doi.org/10.1002/bies.201000037
PubMed:View item in PubMed

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