Detection of foreign RNA: implications for RNAi.
RNA interference (RNAi) is an exciting technology with applications in basic research, in elucidation and validation of drug targets, and as a direct therapeutic. In mammalian settings, it is based on the introduction or expression of small interfering RNA (siRNA) that guide the cleavage of a complementary target messenger RNA. While siRNA certainly directs specific silencing of genes in mammalian cells, longer RNA typically used to silence genes in other organisms potently activate mammalian cell defence mechanisms leading to a non-specific halt in translation, to activation of transcription and often, to cell death. Recent research has revealed that siRNA in certain settings can also activate these RNA-responsive pathways. With the recent advances in RNAi technology and its first forays into the in vivo setting now coming to light, it is pertinent to review the cellular response to ribonucleic acids typically used in RNAi methods.
de Veer
Michael J
MJ
Centre for Animal Biotechnology, The University of Melbourne, Victoria, Australia.
Sledz
Carol A
CA
Williams
Bryan R G
BR
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D050838:Interferon Regulatory Factor-3; D007372:Interferons / Q000235:genetics / Q000502:physiology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology; D008954:Models, Biological; D011506:Proteins / Q000235:genetics / Q000502:physiology; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012328:RNA Viruses / Q000235:genetics; D012330:RNA, Double-Stranded / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology; D051193:Toll-Like Receptors; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D019892:eIF-2 Kinase / Q000235:genetics / Q000502:physiology
D004268:DNA-Binding Proteins; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D008562:Membrane Glycoproteins; D011506:Proteins; C431552:RAI1 protein, human; D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D015534:Trans-Activators; D014157:Transcription Factors; D012313:RNA; D007372:Interferons; D019892:eIF-2 Kinase