RNAa is conserved in mammalian cells.
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.


RESULTS
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 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
This 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.
Huang
Vera
V
Helen-Diller Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, USA.
Qin
Yi
Y
Wang
Ji
J
Wang
Xiaoling
X
Place
Robert F
RF
Lin
Guiting
G
Lue
Tom F
TF
Li
Long-Cheng
LC
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D002522:Chlorocebus aethiops; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D011401:Promoter Regions, Genetic; D012313:RNA / Q000235:genetics*; D051381:Rats; D012689:Sequence Homology, Nucleic Acid
D012313:RNA