利用对内生性蛋白响应的RNA操纵子重编程细胞活动(CNS翻译练习)

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  利用对内生性蛋白响应的RNA操纵子重编程细胞活动(CNS翻译练习)

  Abstract

  与细胞固有的通路相互作用的合成遗传原件可以用来改变自然网络以实现新形式的控制和行为。基因网络的操纵被与(细胞的)原生组分无法相互作用而限制。我们描述了一组RNA元件,它们通过偶联增强特定蛋白的丰度,调节RNA剪切来控制靶基因,从而表达克服了这些限制。我们改造了RNA元件使其能在人细胞中通过核因子κB 和Wnt 信号通路感受信号,并通过这些通路产生新的行为,从而构建非侵入性疾病标志物和改变细胞命运。我们的工作提供了一个遗传学平台,它能够构建重编程的感知冲动元件从而自主控制细胞活动。

  Science. 2010 Nov 26;330(6008):1251-5.

  Reprogramming cellular behavior. with RNA controllers responsive to endogenous proteins.

  Culler SJ, Hoff KG, Smolke CD.

  Division of Chemistry and Chemical Engineering, 1200 East California Boulevard, MC 210-41, California Institute of Technology, Pasadena, CA 91125, USA.

  Abstract

  Synthetic genetic devices that interface with native cellular pathways can be used to change natural networks to implement new forms of control and behavior. The engineering of gene networks has been limited by an inability to interface with native components. We describe a class of RNA control devices that overcome these limitations by coupling increased abundance of particular proteins to targeted gene expression events through the regulation of alternative RNA splicing. We engineered RNA devices that detect signaling through the nuclear factor κB and Wnt signaling pathways in human cells and rewire these pathways to produce new behaviors, thereby linking disease markers to noninvasive sensing and reprogrammed cellular fates. Our work provides a genetic platform. that can build programmable sensing-actuation devices enabling autonomous control over cellular behavior.


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