Double-stranded RNA and interferon-alpha induce transcription through different molecular mechanisms.
Double-stranded (ds) RNA stimulates the synthesis of several mRNAs known to be induced by type I interferons (IFNs). In this report, it is shown that the IFN-alpha stimulated genes (ISGs) 15, 54, 56, and GBP are transcriptionally induced by dsRNA. Transcriptional stimulation occurred in the presence of the protein synthesis inhibitor cycloheximide (CHX), indicating that inducibility was directly mediated by dsRNA through the action of preformed proteins. ISGF-3, the protein complex mediating primary transcriptional induction of ISGs by IFN-alpha, was not activated by dsRNA in the presence of CHX. Additionally, DNA-binding activity of ISGF-2/IRF-1, a protein involved in the regulation of the IFN-beta gene and ISGs, did not correlate with dsRNA-induced transcriptional induction of ISGs. This suggests that dsRNA and IFN-alpha induce ISGs through different molecular mechanisms.
Decker
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Fraunhofer Institute for Toxicology and Molecular Biology, Hannover, Germany.
D003513:Cycloheximide / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019204:GTP-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000494:pharmacology*; D012097:Repressor Proteins; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; C494229:IRF2 protein, human; C494227:IRF9 protein, human; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha; D010750:Phosphoproteins; D012330:RNA, Double-Stranded; D012097:Repressor Proteins; D014157:Transcription Factors; D007371:Interferon-gamma; D003513:Cycloheximide; D019204:GTP-Binding Proteins; D019206:GTP-Binding Protein alpha Subunits, Gi-Go