Bunyavirus mRNA synthesis is coupled to translation to prevent premature transcription termination

Messenger RNA transcription by Bunyaviridae family members is unique within the group of negative-strand RNA viruses as it requires on-going protein synthesis. The long-standing model explaining this phenomenon proposes that the translational requirement is not for a protein product, but instead is for ribosomal translocation along nascent mRNAs. This movement is proposed to disrupt spurious transcription termination signals that otherwise cause premature mRNA truncation leading to a fatal loss of gene expression. This model was tested by introducing translational stop codons into model RNA genomes of Bunyamwera virus, the prototypic member of the Bunyaviridae family. This directly showed that translation of nascent mRNAs prevents transcription termination. While such coupling of transcription and translation is common in prokaryotic systems, these results represent the first report of such obligatory coupling in a eukaryotic cell environment. The results also provide insight into the bunyavirus termination mechanism and suggest it is mechanistically similar to prokaryotic intrinsic termination.