Effect of viral infections on the activity of cellular RNAs

During earlier work we characterized a set of predominantly nuclear proteins, which in cells infected with the positive-strand RNA viruses HCV (human hepatitis C virus) or BVDV (bovine viral diarrhea virus) are specifically sequestered to the sites of viral replication in the cytoplasm. These so-called NF/NFAR proteins bind to defined RNA motifs in the non-translated regions of both viral genomes, and there is evidence that the proteins support the coordination of viral protein and RNA synthesis. In naive cells, the prototype NF/NFAR protein, NF90/NFAR-1 (ILF3, DRBP76), is known to stabilize certain mRNAs increasing their translation. Preliminary data moreover indicate that NF90/NFAR-1 is involved in miRNA biogenesis and/or function. The intriguing scenario that replicating viral RNAs sequester proteins that regulate the activity of cellular RNAs is fuelled by recent data showing that the rate of viral recruitment of NF/NFAR proteins correlates with cell pathology. This application aims at understanding whether viral sequestration of NF90/NFAR-1 affects the activity of natural cellular RNA targets of this protein. Thus, we anticipate obtaining insights into how RNA viruses shape cellular gene expression. On top, we expect gaining further clues on cellular functions of NF90/NFAR-1, particularly in view of its suspected role in miRNA function.