RNAa Is Conserved in Mammalian Cells

PLoS One

Yi Qin¹  Xiaoling Wang¹  Long-Cheng Li¹  Guiting Lin¹  Ji Wang²  Tom F. Lue²  Vera Huang²  Robert F. Place² 

[1] Department of Urology, University of California San Francisco, San Francisco, California, United States of America;Helen-Diller Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, United States of America

关键词: Primates;    Double stranded RNA;    Chimpanzees;    Gene expression;    DNA methylation;    Transfection;    Sequence alignment;    DNA transcription;   

DOI  :  10.1371/journal.pone.0008848

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

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 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/Significance 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.

【 授权许可】

CC BY