Paige, J.S. et al. Science 335, 1194 (2012).

Small-molecule sensors for live imaging studies are relatively few. To add to the toolbox, Paige et al. propose a method that couples small-molecule binding RNA aptamers—short sequences that can be selected in vitro for desirable binding properties—to a conditional fluorophore. The group previously engineered Spinach, an aptamer that causes a modified fluorophore from GFP to fluoresce upon binding. Destabilizing one stem of a stem-loop in Spinach caused it to stop functioning, but attaching a small molecule–binding aptamer sequence to the stem resulted in a reporter that was structured when bound by the small molecule and caused the fluorophore to fluoresce. The group generated Spinach-based sensors for adenosine 5'-diphosphate (ADP), S-adenosylmethionine (SAM) and other molecules in Escherichia coli in this way.