RNAa is conserved in mammalian cells.
RNAa is conserved in mammalian cells.
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DOI：
10.1371/journal.pone.0008848
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发表时间：
2010-01-22
期刊：
影响因子：
3.7
通讯作者：
Li LC
中科院分区：
文献类型：
--
作者：
Huang V;Qin Y;Wang J;Wang X;Place RF;Lin G;Lue TF;Li LC
RNA激活（RNAa）是一种新发现的由小双链RNA（saRNA）触发的基因激活机制。到目前为止，RNA仅在人类细胞中得到证实，尚不清楚它是否在其他哺乳动物中保守。在本研究中，我们评估了RNA在细胞中来自四种哺乳动物物种，包括非人灵长类动物（非洲绿色猴和黑猩猩），小鼠和大鼠。之前，我们鉴定了导致人类细胞中E-钙粘蛋白、p21和VEGF活化的saRNA。由于靶序列在灵长类动物中高度保守，因此将每个人saRNA转染到非洲绿色猴（COS 1）和黑猩猩（WES）细胞中也导致了预期基因的诱导。还设计了靶向临床相关基因（包括p53、PAR 4、WT 1、RB 1、p27、NKX 3 -1、VDR、IL 2和pS2）的其他saRNA，并转染到COS 1和WES细胞中。在这9个基因中，p53、PAR 4、WT 1和NKX 3 -1由其相应的saRNA诱导。我们进一步将RNAa的分析扩展到啮齿动物细胞类型。我们鉴定了两种saRNA，其诱导NIH/3 T3和TRAMP C1细胞中小鼠细胞周期蛋白B1的表达，这导致组蛋白H3的磷酸化增加，组蛋白H3是染色体浓缩和进入有丝分裂的下游标志物。我们还鉴定了两种在原代大鼠脂肪源性干细胞中激活CXCR 4表达的saRNA。这项研究表明，RNA存在于哺乳动物物种而不是人类。我们的研究结果还表明，非人灵长类动物疾病模型可能具有验证基于RNA的药物的临床适用性。
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. 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. 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.
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影响因子：
5.4
作者：
DApuzzo, M;Rolink, A;Moser, B
通讯作者：
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影响因子：
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作者：
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DOI：
10.1073/pnas.0707594105
发表时间：
2008-02-05
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