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Upstream open reading frames: Molecular switches in (patho)physiology
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...
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Formato: | Texto |
Lenguaje: | English |
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WILEY-VCH Verlag
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3045505/ https://www.ncbi.nlm.nih.gov/pubmed/20726009 http://dx.doi.org/10.1002/bies.201000037 |
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author | Wethmar, Klaus Smink, Jeske J Leutz, Achim |
author_facet | Wethmar, Klaus Smink, Jeske J Leutz, Achim |
author_sort | Wethmar, Klaus |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-3045505 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | WILEY-VCH Verlag |
record_format | MEDLINE/PubMed |
spelling | pubmed-30455052011-03-02 Upstream open reading frames: Molecular switches in (patho)physiology Wethmar, Klaus Smink, Jeske J Leutz, Achim Bioessays Prospects & Overviews 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. WILEY-VCH Verlag 2010-10 /pmc/articles/PMC3045505/ /pubmed/20726009 http://dx.doi.org/10.1002/bies.201000037 Text en Copyright © 2010 WILEY Periodicals, Inc. http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation. |
spellingShingle | Prospects & Overviews Wethmar, Klaus Smink, Jeske J Leutz, Achim Upstream open reading frames: Molecular switches in (patho)physiology |
title | Upstream open reading frames: Molecular switches in (patho)physiology |
title_full | Upstream open reading frames: Molecular switches in (patho)physiology |
title_fullStr | Upstream open reading frames: Molecular switches in (patho)physiology |
title_full_unstemmed | Upstream open reading frames: Molecular switches in (patho)physiology |
title_short | Upstream open reading frames: Molecular switches in (patho)physiology |
title_sort | upstream open reading frames: molecular switches in (patho)physiology |
topic | Prospects & Overviews |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3045505/ https://www.ncbi.nlm.nih.gov/pubmed/20726009 http://dx.doi.org/10.1002/bies.201000037 |
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