serval:BIB_FC312387223F
Genomic determinants of the efficiency of internal ribosomal entry sites of viral and cellular origin
10.1093/nar/gkn812
000261299700023
18978018
Kazadi
K.
author
Loeuillet
C.
author
Deutsch
S.
author
Ciuffi
A.
author
Muñoz
M.
author
Beckmann
J.S.
author
Moradpour
D.
author
Antonarakis
S.E.
author
Telenti
A.
author
article
2008
Nucleic Acids Research
1362-4962
journal
36
21
6918-25
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.
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
eng
60_published
true
peer-reviewed
University of Lausanne
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