This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: This work was supported by Ministry of Education, Culture, Sports, Science and Technology (MEXT) Grants-in-aid for Scientific Research on Priority Areas (Infection and Host Responses Matrix of Infection Phenomena) and PRESTO from Japan Science and Technology Agency (JST). Received: MaAccepted: OctoPublished: November 6, 2009Ĭopyright: © 2009 Watanabe et al. Basler, Mount Sinai School of Medicine, United States of America
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Our findings uncover not only a unique translational control of viral regulatory protein but also a previously unknown mechanism of translational regulation of polycistronic mRNA using RNA helicases.Ĭitation: Watanabe Y, Ohtaki N, Hayashi Y, Ikuta K, Tomonaga K (2009) Autogenous Translational Regulation of the Borna Disease Virus Negative Control Factor X from Polycistronic mRNA Using Host RNA Helicases. We demonstrate that host RNA helicases, mainly DDX21, can affect ribosomal reinitiation of X via interaction with the 5′ untranslated region (UTR) of X/P mRNA and that the downstream P protein autogenously controls the translation of X by interfering with the binding of DDX21 to the 5′ UTR. In this study, we show an ingenious strategy of translational control of viral regulatory protein using host factors. Although BDV X and P have opposing effects in terms of viral polymerase activity, the translational regulation of X/P polycistronic mRNA has not been elucidated. Among them, the 0.8 kb X/P mRNA encodes at least three open reading frames (ORFs), upstream ORF, X, and P. BDV expresses mRNAs as polycistronic coding transcripts.
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Borna disease virus (BDV) is a highly neurotropic RNA virus which is characterized by persistent infection.
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Translation regulation of viral mRNA is a good example of this. Therefore, the replication strategies of viruses may provide not only the understanding of virus pathogenesis but also useful models to disentangle the complex machinery of host cells. Our results not only demonstrate a unique translational control of viral regulatory protein, but also elucidate a previously unknown mechanism of regulation of polycistronic mRNA translation using RNA helicases.Īll viruses rely on host cell factors to complete their life cycles. We found that P may enhance ribosomal reinitiation at the X ORF by inhibition of the interaction of the DEAD-box RNA helicase DDX21 with the 5′ untranslated region of X/P mRNA, via interference with its phosphorylation. Transient transfection of cDNA clones corresponding to the X/P mRNA revealed that the X ORF is translated predominantly by uORF-termination-coupled reinitiation, the efficiency of which is upregulated by expression of P. Here we demonstrate that the X/P mRNA autogenously regulates the translation of X via interaction with host factors. However, the translation mechanism used by the X/P polycistronic mRNA has not been determined in detail. The X is a negative regulator of viral polymerase activity, while the P phosphoprotein is a necessary cofactor of the polymerase complex, suggesting that the translation of X is controlled rigorously, depending on viral replication. The shortest transcript of BDV, X/P mRNA, encodes at least three open reading frames (ORFs): upstream ORF (uORF), X, and P in the 5′ to 3′ direction. Borna disease virus (BDV) is a nonsegmented, negative-strand RNA virus that employs several unique strategies for gene expression.