An Oncogenic RNA?

Repellin, C. and Wilson, J.B. (2005) An Oncogenic RNA? 70th Cold Spring Harbor Symposium: Molecular Approaches to Controlling Cancer, Cold Spring Harbor, NY, USA, 28 May - 02 Jun 2005.

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Burkitt’s lymphoma (BL), Hodgkin’s disease and nasopharyngeal carcinoma are human cancers associated with Epstein-Barr Virus (EBV). In these cancers, a different subset of the viral latent genes are expressed, but all express EBV small polymerase III (pol III) non-translated RNAs: EBER1 and EBER2. The EBERs confer resistance to interferon (IFN)-α-induced apoptosis via binding of the IFN-inducible, double-stranded RNA-activated protein kinase PKR and inhibition of its activation by phosphorylation. Recent evidence has suggested an oncogenic role of the EBERs in BL cells, indicating their possible contribution to the disease process of EBV-associated tumours. In order to investigate the potential role of EBER1 as an oncogenic RNA, we have generated 14 lines of transgenic mice designed to express EBER1 in lymphoid cells using three variant transgenes. The transgenes incorporate a novel combination of tissue-specific RNA pol II and pol III elements. The efficacy of transgene expression has been confirmed in culture. To date, mice of 5 of the transgenic lines have been shown to express EBER1 specifically in lymphoid tissues. Further lines are currently under test. Mice expressing EBER1 are viable, with the phenotypic consequences of EBER1 expression in vivo under examination. A cross-breeding programme is being conducted between EμEBER1 and Eμmyc transgenic mice. Tumour incidence is being monitored and begins to show a possible cooperation between EBER1 and myc in tumour onset and pathology. This would suggest that EBER1 has oncogenic properties, the first pol III RNA described as such. This would implicate the RNA in the pathogenesis of EBV associated lymphoma as well as its role in immune evasion.

Item Type:Conference or Workshop Item
Glasgow Author(s) Enlighten ID:Wilson, Professor Joanna
Authors: Repellin, C., and Wilson, J.B.
Subjects:Q Science > QR Microbiology > QR355 Virology
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences
College of Medical Veterinary and Life Sciences > School of Molecular Biosciences

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