Intelligent ribozyme that switches its activity in response to K^+ through quadruplex formation
Intelligent ribozyme that switches its activity in response to K^+ through quadruplex formation
复制标题
智能核酶，通过四链体形成响应 K^ 来切换其活性
DOI：
10.1111/j.1742-4658.2012.08538.x
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发表时间：
2012
期刊：
影响因子：
5.4
通讯作者：
M.
中科院分区：
文献类型：
--
作者：
Nagata;T.;Sakurai;Y.;Hara;Y.;Mashima;T.;Kodaki;T.;Katahira;M.
对K+的响应，r(GGAGGAGGAGGA)(R12)的结构由单链结构转变为紧密的四链结构。在锤头状核酶中，催化核心的两个部分与茎相连，并位于非常接近的位置以发挥活性。在本研究中，茎被R12(或R11，缺少A末端残基)取代，带有或不带有连接子残基。其中一个新构建的核酶表现出对K+的反应活性增强，我们认为四链的形成恢复了活性催化核心。其他核酶对K+的反应表现出抑制活性，这表明活性核心的形成被阻止了。因此，我们已经成功地开发出其活性在K+反应中被抑制或增强的“智能”核酶。由于细胞内和细胞外K+浓度的差异，这种转换能力可能具有治疗应用。
The structure of r(GGAGGAGGAGGA) (R12) changes from a single‐stranded form to a compact quadruplex one in response to K+. In a hammerhead ribozyme, two portions of the catalytic core are linked with the stem and are located in close proximity in order to exert activity. In this study, the stem was replaced by R12 (or R11, which lacks the terminal A residue) with or without linker residues. One of the newly constructed ribozymes exhibited enhanced activity in response to K+, and we suggest that quadruplex formation restored the active catalytic core. Other ribozymes exhibited repressed activity in response to K+, suggesting that formation of the active core was prevented. Thus, we have succeeded in developing ‘intelligent’ ribozymes whose activity is either repressed or enhanced in response to K+. This switching capability may have therapeutic applications because of the differences between intra‐ and extracellular K+concentrations.