A comprehensive view of regulation of gene expression by double-stranded RNA-mediated cell signaling

Double-stranded (ds) RNA, a common component of virus-infected cells, is a potent inducer of the type I interferon and other cellular genes. For ident ifying the full repertoire of human dsRNA-regulated genes, a cDNA microarra y hybridization screening was conducted using mRNA from dsRNA-treated GRE c ells. Because these cells lack all type I interferon genes, the possibility of gene induction by autocrine actions of interferon was eliminated. Our s creen identified 175 dsRNA-stimulated genes (DSG) and 95 dsRNA-repressed ge nes.. A subset of the DSGs was also induced by different inflammatory cytok ines and viruses demonstrating interconnections among disparate signaling p athways. Functionally, the DSGs encode proteins involved in signaling, apop tosis, RNA synthesis, protein synthesis and processing, cell metabolism, tr ansport, and structure. Induction of such a diverse family of genes by dsRN A has major implications in host-virus interactions and in the use of RNA, technology for functional ablation of specific, genes.