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

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Serval ID
serval:BIB_FC312387223F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genomic determinants of the efficiency of internal ribosomal entry sites of viral and cellular origin
Journal
Nucleic Acids Research
Author(s)
Kazadi K., Loeuillet C., Deutsch S., Ciuffi A., Muñoz M., Beckmann J.S., Moradpour D., Antonarakis S.E., Telenti A.
ISSN
1362-4962
Publication state
Published
Issued date
2008
Peer-reviewed
Oui
Volume
36
Number
21
Pages
6918-25
Language
english
Abstract
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.
Keywords
5' Untranslated Regions, Cell Line, Encephalomyocarditis virus, Genome-Wide Association Study, Humans, Linkage (Genetics), Protein Biosynthesis, Proto-Oncogene Proteins c-myc, Quantitative Trait Loci, RNA, Viral, X-Linked Inhibitor of Apoptosis Protein
Pubmed
Web of science
Open Access
Yes
Create date
22/01/2009 11:55
Last modification date
20/08/2019 16:27
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