Double-Stranded RNA and Interferon-α Induce Transcription Through Different Molecular Mechanisms

Abstract

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-a 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-α, 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-β gene and ISGs, did not correlate with dsRNA-induced transcriptional induction of ISGs. This suggests that dsRNA and IFN-α induce ISGs through different molecular mechanisms.