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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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Detalles Bibliográficos
Autores principales: Wethmar, Klaus, Smink, Jeske J, Leutz, Achim
Formato: Texto
Lenguaje:English
Publicado: WILEY-VCH Verlag 2010
Materias:
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.
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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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