Artificial Riboswitches: Synthetic mRNA‐Based Regulators of Gene Expression
Artificial Riboswitches: Synthetic mRNA‐Based Regulators of Gene Expression
复制标题
人工核糖开关：基于合成 mRNA 的基因表达调节剂
DOI：
10.1002/cbic.200800154
复制
发表时间：
2008
期刊：
影响因子：
3.2
通讯作者：
J. Hartig
中科院分区：
文献类型：
--
作者：
Markus Wieland;J. Hartig
半个世纪以来，已知细菌基因表达的调节由与代谢物相互作用的蛋白质主导，这导致转录起始的改变。尽管大多数基因的表达是由基于蛋白质的机制控制的，但基于RNA的反馈装置的发现令人惊讶，该反馈装置能够在不需要参与蛋白质的情况下调节表达。Breaker及其同事最初发现，这种称为核糖开关的机制在细菌中广泛使用。对于突出天然存在的核糖开关的优秀评论，我们参考了最近的文献。核糖开关通常位于细菌mRNA的5 '-非翻译区（5'-UTR）中，并且主要由特异性感测代谢物的第一结构域（称为适体结构域）和通过结构重排促进对转录终止或翻译起始的控制的第二结构域（表达平台）组成（参见方案1）。关于Breaker及其同事的革命性发现，非常有趣的是，研究人员甚至在天然核糖开关被发现之前几年就成功地构建了类似的人工系统。这种人造的基于RNA的调节剂的产生是可能的，通过使用适配体技术来识别RNA的配体。适体是特异性结合所选配体的体外选择的核酸序列。这种基于RNA的人工开关能够控制基因表达，与内在代谢解耦。虽然天然的核糖ACHTUNGTRENNUNG开关主要存在于细菌中，但人工系统也已被构建用于真核生物。这种量身定制的监管装置应证明是生物技术和合成生物学应用中的有价值的工具。在这里，我们给出了不同的概念，是基于插入的配体传感元件到mRNA的概述，从而使各自的信息的表达调控。由于篇幅的限制，我们将不讨论人工反式作用机制，如小分子调控的，基于RNA的转录激活因子，也没有配体控制的反义结构的基因表达的调控。
For half a century, bacterial regulation of gene expression has been known to be dominated by proteins that interact with metabolites, which results in altered transcription initiation. lthough the expression of the majority of genes is controlled by protein-based mechanisms, the discovery of RNA-based feedback devices that enable regulation of expression without the need for engaged proteins came as a surprise. Breaker and co-workers initially discovered that the use of such mechanisms, termed riboswitches, is widespread in bacteria. For excellent reviews that highlight naturally occurring riboswitches, we refer to the recent literature. Riboswitches are typically located in the 5’-untranslated region (5’-UTR) of bacterial mRNA, and consist mainly of a first domain (called aptamer domain) that specifically senses a metabolite, and a second domain (the expression platform) that facilitates control over transcription termination or translation initiation by a structural rearrangement (see Scheme 1). With respect to the revolutionary findings of Breaker and coworkers, it is very intriguing that researchers have successfully constructed similar, artificial systems even several years before naturally occurring riboswitches were discovered. The generation of such man-made, RNA-based regulators was possible by using aptamer technology for the recognition of ligands by RNAs. Aptamers are in-vitro-selected nucleic acid sequences that specifically bind to a ligand of choice. Such artificial, RNA-based switches enable the control of gene expression, uncoupled from the intrinsic metabolism. Although natural riboACHTUNGTRENNUNGswitches are mainly found in bacteria, artificial systems have been constructed for eukaryotic organisms as well. Such tailormade regulatory devices should prove of value as tools in biotechnology as well as synthetic biology applications. Here, we give an overview of the different concepts that are based on the insertion of ligand-sensing elements into mRNAs, thereby enabling the regulation of expression of the respective message. Due to space restrictions we will neither discuss artificial trans-acting mechanisms such as small-molecule-regulated, RNA-based transcriptional activators, nor ligand-controlled antisense constructs for the regulation of gene expression.
影响因子：
56.9
作者：
TUERK, C;GOLD, L
通讯作者：
GOLD, L