Autogenous translational regulation of the Borna disease virus negative control factor X from polycistronic mRNA using host RNA helicases.
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.
Watanabe
Yohei
Y
Department of Virology, Research Institute for Microbial Diseases (BIKEN), Osaka University, Suita, Osaka, Japan.
Ohtaki
Naohiro
N
Hayashi
Yohei
Y
Ikuta
Kazuyoshi
K
Tomonaga
Keizo
K
D001891:Borna disease virus / Q000235:genetics*; D015967:Gene Expression Regulation, Viral; D054884:Host-Pathogen Interactions; D020365:RNA Helicases / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics*
D012367:RNA, Viral; D054334:Viral Regulatory and Accessory Proteins; D020365:RNA Helicases