Prospects & Overviews
Upstream open reading frames: Molecular switches in (patho)physiology
Version of Record online: 19 AUG 2010
Copyright © 2010 WILEY Periodicals, Inc.
Volume 32, Issue 10, pages 885–893, October 2010
How to Cite
Wethmar, K., Smink, J. J. and Leutz, A. (2010), Upstream open reading frames: Molecular switches in (patho)physiology. Bioessays, 32: 885–893. doi: 10.1002/bies.201000037
- Issue online: 13 SEP 2010
- Version of Record online: 19 AUG 2010
- Funded Access
- translational control;
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 β (C/EBPβ) gene resulted in deregulated C/EBPβ 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.