Efficient translation of rotavirus mRNA requires simultaneous interaction of NSP3 with the eukaryotic translation initiation factor eIF4G and the mRNA 3 ' end

In contrast to the vast majority of cellular proteins, rotavirus proteins a re translated from capped but nonpolyadenylated mRNAs. The viral nonstructu ral protein NSP3 specifically binds the 3'-end consensus sequence of viral mRNAs and interacts with the eukaryotic translation initiation factor eIP4G . Here,ve show that expression of NSP3 in mammalian cells allows the effici ent translation of virus-like mRNA. A synergistic effect between the cap st ructure and the 3' end of rotavirus mRNA was observed in NSP3-expressing ce lls. The enhancement of viral mRNA translation by NSP3 was also observed in a rabbit reticulocyte lysate translation system supplemented with recombin ant NSP3. The use of NSP3 mutants indicates that its RNA- and eIF4G-binding domains are both required to enhance the translation of viral mRNA The res ults reported here show that NSP3 forms a link between viral mRNA and the c ellular translation machinery and hence is a functional analogue of cellula r poly(A)-binding protein.