Short dsRNAs targeting promoter sequences induce WT1 gene expression Free

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Small double-stranded RNAs (dsRNAs), such as microRNAs (miRNAs) and small interfering RNAs (siRNAs), are known to silence homologous sequences through multiple mechanisms. However, our lab has recently reported a new phenomenon in which small synthetic dsRNAs targeting promoter regions readily induce gene expression in human cells. To identify more candidate genes susceptible to dsRNA-induced gene activation (RNAa), we designed and synthesized 21-nt dsRNAs targeting regions in the promoter of the tumor suppressor gene Wilms’ Tumor 1 (WT1). Transfection of these dsRNAs into human cell lines induced the expression of WT1. Interestingly, dsRNA transfection also induced the expression of an upstream neighboring gene WIT1 that is transcribed in the opposite direction as WT1. Cells treated with WT1 dsRNA also acquired phenotypes associated with WT1 overexpression, including increased apoptosis. These findings reveal yet another gene susceptible to RNAa and further hint at the potential therapeutic use for dsRNA in targeted gene activation.