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Autogenous translational regulation of the Borna disease virus negative control factor X from polycistronic mRNA using host RNA helicases.

ABSTRACT: Borna disease virus (BDV) is a nonsegmented, negative-strand RNA virus that employs several unique strategies for gene expression. 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. 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. However, the translation mechanism used by the X/P polycistronic mRNA has not been determined in detail. Here we demonstrate that the X/P mRNA autogenously regulates the translation of X via interaction with host factors. 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. 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. 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.

SUBMITTER: Watanabe Y

PROVIDER: S-EPMC2766071 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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Autogenous translational regulation of the Borna disease virus negative control factor X from polycistronic mRNA using host RNA helicases.

Watanabe Yohei Y Ohtaki Naohiro N Hayashi Yohei Y Ikuta Kazuyoshi K Tomonaga Keizo K

PLoS pathogens 20091106 11

Borna disease virus (BDV) is a nonsegmented, negative-strand RNA virus that employs several unique strategies for gene expression. 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. 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 ...[more]

PMID: 19893625

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Dataset Information

Autogenous translational regulation of the Borna disease virus negative control factor X from polycistronic mRNA using host RNA helicases.

Publications

Autogenous translational regulation of the Borna disease virus negative control factor X from polycistronic mRNA using host RNA helicases.

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