Activation of IRF3 by siRNA. Long dsRNA, siRNA, or miRNAs can activate interferon regulatory factor 3 (IRF3) via Toll-like receptor 3 (TLR3)–dependent or –independent pathways via noncanonical kinases TBK1 or IKKe or the canonical kinase complex IKK, resulting in transcriptional up-regulation of interferons and other primary response genes.