Systematic and Comprehensive Analysis of Interferon Response induced by siRNA

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In mammalian cells, siRNAs have been used to induce RNA interference (RNAi) in an attempt to prevent nonspecific effects (including the interferon (IFN) response) which are caused by long double-stranded RNAs (dsRNAs) of more than 30 bp. In this project, we developed a novel and simple strategy for avoiding activation of the IFN response by dsRNA, and analyzed interferon pathway by means of siRNA library. We showed that modified hairpin-RNAs (mhRNAs) of more than 100 bp, with multiple specific point-mutations within the sense strand and transcribed from the U6 or tRNAVa1 promoters, can cause RNAi without inducing the IFN pathway genes. These findings should enhance the exploitation of RNAi in mammalian cells, especially in the field of RNAi therapy against pathogenic viruses. Furthermore the results from screening by siRNA library showed that apoptosis pathway induced by dsRNA include a JNK/SAPK-mediated mitochondrial pathway and an ERK2-related pathway.