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  • Original Paper
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Epstein–Barr virus U leader exon contains an internal ribosome entry site

Oncogene volume 22, pages 572–581 (2003)Cite this article

Abstract

Eukaryotic translation can be initiated either by a cap-dependent mechanism or by internal ribosome entry, a process by which ribosomes are directly recruited to structured regions of mRNA upstream of the initiation codon. Here we report the finding of an internal ribosome entry site (IRES) in the untranslated region of the Epstein–Barr nuclear antigen 1 (EBNA1) gene. EBNA1 is the only nuclear protein expressed in all known states of Epstein–Barr virus (EBV) latency and in the virus lytic cycle, and is required for the maintenance of the EBV episome. Using cDNA reporter constructs and in vitro transfection assays, we found that sequences contained in the 5′ untranslated region (UTR) of the Fp and Qp initiated EBNA1 mRNA increased the expression level 4–14- fold in different Burkitt lymphoma cell lines. The U leader exon, located within the 5′ UTR, included in all known EBNA1 transcripts and also contained in the EBNA3, 4 and 6 mRNAs, was demonstrated by bicistronic expression analyses to contain an IRES. The EBNA IRES initiates translation more efficiently than the encephalomyocarditis virus IRES in EBV-positive lymphoma cells. We propose that the EBNA IRES constitute a novel mechanism, whereby EBV regulates latent gene expression.

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Acknowledgements

We thank Ann Jansson, Henrik Zetterberg and Tore Samuelsson for valuable discussions. This study, Assar Jahrielsson Fund was supported by grants from the Swedish Cancer Society and the LUA research fund, Sahlgrenska University Hospital.

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  1. Department of Clinical Chemistry and Transfusion Medicine, Institute of Laboratory Medicine, Sahlgrenska University Hospital, Göteborg University, Gothenburg, S-413 45, Sweden

    Åsa Isaksson, Malin Berggren & Anne Ricksten

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  1. Åsa Isaksson
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  2. Malin Berggren
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  3. Anne Ricksten
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Correspondence to Anne Ricksten.

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Isaksson, Å., Berggren, M. & Ricksten, A. Epstein–Barr virus U leader exon contains an internal ribosome entry site. Oncogene 22, 572–581 (2003). https://doi.org/10.1038/sj.onc.1206149

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