Conformational Shannon entropy of mRNA structures from force spectroscopy measurements predicts the efficiency of -1 programmed ribosomal frameshift stimulation

Abstract

-1 Programmed ribosomal frameshifting (-1 PRF) is stimulated by structures in mRNA, but the factors determining -1 PRF efficiency are unclear. We show that -1 PRF efficiency varies directly with the conformational heterogeneity of the stimulatory structure, quantified as the Shannon entropy of the state occupancy, for a panel of stimulatory structures with efficiency ranging from 2-80%. The correlation is force-dependent and vanishes at forces above those applied by the ribosome. This work supports the hypothesis that heterogeneous conformational dynamics are a key factor in stimulating -1 PRF.