Regulatory RNA induces the production of IFN-γ, but not IL-4 in human lymphocytes:: Role of RNA-dependent protein kinase (PKR) and NF-κB

Previous results with p9-RNA, obtained from lymph nodes of animals immunized with the peptide p9 of HIV-1, suggested that its effects on lymphocytes could be mediated by RNA-dependent protein kinase (PKR). Here we report that p9-RNA activates PKR leading to the degradation of the inhibitor I-kappaBalpha and the concomitant nuclear factor kappa B (NF-kappaB) activation. The fractionation of p9-RNA by affinity chromatography indicates that the poly A(+) p9-RNA is the fraction responsible for PKR activation. We also found that p9-RNA induces the production of interferon-gamma (IFN-gamma), but not interleukin (IL-4) since only IFN-gamma gene promoter contains NF-kappaB binding site. This study provides the first evidence that transcriptional control of gene expression by regulatory RNAs can be mediated by PKR through NF-kappaB activation. A model for the mechanism of action of poly A(+) p9-RNA is proposed.