'Intelligent' ribozyme whose activity is altered in response to K+ as a result of quadruplex formation

Abstract

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.