Tradeoffs in the design of RNA thermometers

Abstract

The synthesis of RNA thermometers is aimed at achieving temperature responses with desired thresholds and sensitivities. Although previous works have generated thermometers with a variety of thresholds and sensitivities as well as guidelines for design, possible constraints in the achievable thresholds and sensitivities remain unclear. We addressed this issue using a two-state model and its variants, as well as melt profiles generated from thermodynamic computations. In the two-state model, we found that the threshold was inversely proportional to the sensitivity, in the case of a fixed energy difference between the two states. Notably, this constraint could persist in variations of the two-state model with sequentially unfolding states and branched parallel pathways. Furthermore, the melt profiles generated from a library of thermometers exhibited a similar constraint. These results should inform the design of RNA thermometers as well as other responses that are mediated in a similar fashion.