Skip Navigation



Nucleic Acids Research Advance Access published online on October 31, 2008
Nucleic Acids Research, doi:10.1093/nar/gkn812
This Article
Right arrow Full Text Freely available
Right arrow Print PDF (828K) Freely available
Right arrow Screen PDF (272K) Freely available
Right arrow Supplementary Data
Right arrowOA All Versions of this Article:
36/21/6918    most recent
gkn812v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Kazadi, K.
Right arrow Articles by Telenti, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kazadi, K.
Right arrow Articles by Telenti, A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2008 The Author(s)
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.

Genomics

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

Kayole Kazadi1, Corinne Loeuillet1, Samuel Deutsch2, Angela Ciuffi1, Miguel Muñoz1, Jacques S. Beckmann3, Darius Moradpour4, Stylianos E. Antonarakis2 and Amalio Telenti1,*

1Institute of Microbiology, University Hospital Center and University of Lausanne, 2Division of Medical Genetics, University of Geneva, 3Department of Medical Genetics and 4Division of Gastroenterology and Hepatology, University Hospital Center and University of Lausanne, Switzerland

*To whom correspondence should be addressed. Tel: +41 21 314 0550; Fax: +41 21 314 4095; Email: amalio.telenti{at}chuv.ch

Received September 17, 2008. Revised October 3, 2008. Accepted October 10, 2008.

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 (h2 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.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Nucleic Acids ResHome page
M. Vallejos, P. Ramdohr, F. Valiente-Echeverria, K. Tapia, F. E. Rodriguez, F. Lowy, J. P. Huidobro-Toro, J. A. Dangerfield, and M. Lopez-Lastra
The 5'-untranslated region of the mouse mammary tumor virus mRNA exhibits cap-independent translation initiation
Nucleic Acids Res., November 4, 2009; (2009) gkp890v1.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.