Abstract
BackgroundRNA 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 FindingsIn 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 histone H3, a downstream marker for chromosome condensation and entry into mitosis. We also identified two saRNAs that activated the expression of CXCR4 in primary rat adipose–derived stem cells.Conclusions/SignificanceThis study demonstrates that RNAa exists in mammalian species other than human. Our findings also suggest that nonhuman primate disease models may have clinical applicability for validating RNAa-based drugs.
Highlights
RNA activation (RNAa) is a newly discovered mechanism of gene activation directed by small double-stranded RNAs [1,2,3]
We previously identified small activating RNAs’ (saRNAs) that activated that expression of E-cadherin, p21, and VEGF in human cells [1]
Conservation was confirmed by sequencing DNA amplified from non-human primate COS1 (African green monkey, AGM) and WES cell lines (Fig. 1, GenBank accession numbers for the resulted sequences are listed in Materials and Methods)
Summary
RNA activation (RNAa) is a newly discovered mechanism of gene activation directed by small double-stranded RNAs (dsRNAs) [1,2,3]. These dsRNAs, termed ‘small activating RNAs’ (saRNAs), exert an effect opposite to that of RNA-interference (RNAi). Small RNAs have been shown to enhance post-transcriptional gene expression by directly promoting translation [8] or antagonizing miRNA target recognition [9]. Regardless, what is becoming clear is that RNAa has potential to be exploited to induce the expression of a variety of genes in human cells. RNA activation (RNAa) is a newly discovered mechanism of gene activation triggered by small doublestranded RNAs termed ‘small activating RNAs’ (saRNAs). RNAa has only been demonstrated in human cells and is unclear whether it is conserved in other mammals
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
