Regulatory RNA induces the production of IFN-gamma, but not IL-4 in human lymphocytes: role of RNA-dependent protein kinase (PKR) and NF-kappaB.
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-kappaB alpha 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.
De Lucca
Fernando L
FL
Department of Biochemistry and Immunology, School of Medicine University of São Paulo, Ribeirão Preto, SP, Brazil. fldlucca@fmrp.usp.br
Sales
Valeria S F
VS
Souza
Liliana R
LR
Murad
Joana M
JM
Watanabe
Maria Angelica E
MA
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D020672:I-kappa B Proteins / Q000187:drug effects / Q000378:metabolism; D007371:Interferon-gamma / Q000187:drug effects / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000187:drug effects / Q000502:physiology*; D011061:Poly A; D012313:RNA / Q000378:metabolism* / Q000494:pharmacology; D014764:Viral Proteins / Q000235:genetics; D019892:eIF-2 Kinase / Q000187:drug effects / Q000502:physiology*
D020672:I-kappa B Proteins; D016328:NF-kappa B; D014764:Viral Proteins; D015847:Interleukin-4; D011061:Poly A; D012313:RNA; D007371:Interferon-gamma; D019892:eIF-2 Kinase