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Genomic determinants of the efficiency of internal ribosomal entry sites of viral and cellular origin

Variation in cellular gene expression levels has been shown to be inherited. Expression is controlled at transcriptional and post-transcriptional levels. Internal ribosome entry sites (IRES) are used by viruses to bypass inhibition of cap-dependent translation, and by eukaryotic cells to control tra...

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Autores principales: Kazadi, Kayole, Loeuillet, Corinne, Deutsch, Samuel, Ciuffi, Angela, Muñoz, Miguel, Beckmann, Jacques S., Moradpour, Darius, Antonarakis, Stylianos E., Telenti, Amalio
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2588522/
https://www.ncbi.nlm.nih.gov/pubmed/18978018
http://dx.doi.org/10.1093/nar/gkn812
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author Kazadi, Kayole
Loeuillet, Corinne
Deutsch, Samuel
Ciuffi, Angela
Muñoz, Miguel
Beckmann, Jacques S.
Moradpour, Darius
Antonarakis, Stylianos E.
Telenti, Amalio
author_facet Kazadi, Kayole
Loeuillet, Corinne
Deutsch, Samuel
Ciuffi, Angela
Muñoz, Miguel
Beckmann, Jacques S.
Moradpour, Darius
Antonarakis, Stylianos E.
Telenti, Amalio
author_sort Kazadi, Kayole
collection PubMed
description Variation in cellular gene expression levels has been shown to be inherited. Expression is controlled at transcriptional and post-transcriptional levels. Internal ribosome entry sites (IRES) are used by viruses to bypass inhibition of cap-dependent translation, and by eukaryotic cells to control translation under conditions when protein synthesis is inhibited. We aimed at identifying genomic determinants of variability in IRES-mediated translation of viral [Encephalomyocarditis virus (EMCV)] and cellular IRES [X-linked inhibitor-of-apoptosis (XIAP) and c-myc]. Bicistronic lentiviral constructs expressing two fluorescent reporters were used to transduce laboratory and B lymphoblastoid cell lines [15 CEPH pedigrees (n = 205) and 50 unrelated individuals]. IRES efficiency varied according to cell type and among individuals. Control of IRES activity has a significant genetic component (h(2) of 0.47 and 0.36 for EMCV and XIAP, respectively). Quantitative linkage analysis identified a suggestive locus (LOD 2.35) on chromosome 18q21.2, and genome-wide association analysis revealed of a cluster of SNPs on chromosome 3, intronic to the FHIT gene, marginally associated (P = 5.9E-7) with XIAP IRES function. This study illustrates the in vitro generation of intermediate phenotypes by using cell lines for the evaluation of genetic determinants of control of elements such as IRES.
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spelling pubmed-25885222009-03-04 Genomic determinants of the efficiency of internal ribosomal entry sites of viral and cellular origin Kazadi, Kayole Loeuillet, Corinne Deutsch, Samuel Ciuffi, Angela Muñoz, Miguel Beckmann, Jacques S. Moradpour, Darius Antonarakis, Stylianos E. Telenti, Amalio Nucleic Acids Res Genomics Variation in cellular gene expression levels has been shown to be inherited. Expression is controlled at transcriptional and post-transcriptional levels. Internal ribosome entry sites (IRES) are used by viruses to bypass inhibition of cap-dependent translation, and by eukaryotic cells to control translation under conditions when protein synthesis is inhibited. We aimed at identifying genomic determinants of variability in IRES-mediated translation of viral [Encephalomyocarditis virus (EMCV)] and cellular IRES [X-linked inhibitor-of-apoptosis (XIAP) and c-myc]. Bicistronic lentiviral constructs expressing two fluorescent reporters were used to transduce laboratory and B lymphoblastoid cell lines [15 CEPH pedigrees (n = 205) and 50 unrelated individuals]. IRES efficiency varied according to cell type and among individuals. Control of IRES activity has a significant genetic component (h(2) of 0.47 and 0.36 for EMCV and XIAP, respectively). Quantitative linkage analysis identified a suggestive locus (LOD 2.35) on chromosome 18q21.2, and genome-wide association analysis revealed of a cluster of SNPs on chromosome 3, intronic to the FHIT gene, marginally associated (P = 5.9E-7) with XIAP IRES function. This study illustrates the in vitro generation of intermediate phenotypes by using cell lines for the evaluation of genetic determinants of control of elements such as IRES. Oxford University Press 2008-12 2008-10-31 /pmc/articles/PMC2588522/ /pubmed/18978018 http://dx.doi.org/10.1093/nar/gkn812 Text en © 2008 The Author(s) http://creativecommons.org/licenses/by-nc/2.0/uk/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Genomics
Kazadi, Kayole
Loeuillet, Corinne
Deutsch, Samuel
Ciuffi, Angela
Muñoz, Miguel
Beckmann, Jacques S.
Moradpour, Darius
Antonarakis, Stylianos E.
Telenti, Amalio
Genomic determinants of the efficiency of internal ribosomal entry sites of viral and cellular origin
title Genomic determinants of the efficiency of internal ribosomal entry sites of viral and cellular origin
title_full Genomic determinants of the efficiency of internal ribosomal entry sites of viral and cellular origin
title_fullStr Genomic determinants of the efficiency of internal ribosomal entry sites of viral and cellular origin
title_full_unstemmed Genomic determinants of the efficiency of internal ribosomal entry sites of viral and cellular origin
title_short Genomic determinants of the efficiency of internal ribosomal entry sites of viral and cellular origin
title_sort genomic determinants of the efficiency of internal ribosomal entry sites of viral and cellular origin
topic Genomics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2588522/
https://www.ncbi.nlm.nih.gov/pubmed/18978018
http://dx.doi.org/10.1093/nar/gkn812
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