rnaa is conserved in mammalian cells在哺乳动物细胞rnaa是守恒的.pdfVIP

RNAa Is Conserved in Mammalian Cells 1,2 1,2 1,2 1,2 1,2 2 2 Vera Huang , Yi Qin , Ji Wang , Xiaoling Wang , Robert F. Place , Guiting Lin , Tom F. Lue , Long- Cheng Li1,2* 1 Helen-Diller Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, United States of America, 2 Department of Urology, University of California San Francisco, San Francisco, California, United States of America Abstract Background: RNA activation (RNAa) is a newly discovered mechanism of gene activation triggered by small double- stranded RNAs termed ‘small activating RNAs’ (saRNAs). Thus far, RNAa has only been demonstrated in human cells and is unclear whether it is conserved in other mammals. Methodology/Principal Findings: In the present study, we evaluated RNAa in cells derived from four mammalian species including nonhuman primates (African green monkey and chimpanzee), mouse, and rat. Previously, we identified saRNAs leading to the activation of E-cadherin, p21, and VEGF in human cells. As the targeted sequences are highly conserved in primates, transfection of each human saRNA into African green monkey (COS1) and chimpanzee (WES) cells also resulted in induction of the intended gene. Additional saRNAs targeting clinically relevant genes including p53, PAR4, WT1, RB1, p27, NKX3-1, VDR, IL2, and pS2 were also designed and transfected into COS1 and WES cells. Of the nine genes, p53, PAR4, WT1, and NKX3-1 were induced by their corresponding saRNAs. We further extended our analysis of RNAa into rodent cell types. We identified two saRNAs that induced the expression of mouse Cyclin B1 in NIH/3T3 and TRAMP C1 cells, which led to increased phosphorylation of hi