%0 Journal Article
%T Thermodynamic Control of Ribosomal Frameshifting
%J -
%D 2019
%R https://doi.org/10.1016/j.bpj.2018.11.1966
%X Ribosomal translation of mRNA proceeds by decoding three nucleotides at a time and spontaneous changes of the reading frame are rare. However, specific mRNA sequences can guide the ribosome to shift the reading frame. Programmed £¿1 ribosomal frameshifting occurs while two tRNAs are bound to a slippery-sequence motif of the mRNA. Mutations of the slippery sequence have dramatic effects on the frameshift efficiency. In this study, employing Bayesian statistics, we build a model to obtain the free energies of the base pairs in the 0 and £¿1 frames. Our results show that the frameshift effciencies can be reproduced and even predicted from the free energies of the tRNA-mRNA base pairs present in both frames. The observation that the free-energy difference determines the probability of ending up in either reading frame indicates that the ribosome is paused to such a degree that the free-energy barrier hindering the change of the reading frame can be overcome. Therefore, frameshifting is controlled by thermodynamics and not by kinetics. Further, the base-pair free energies obtained from our analysis allow us to quantify the effect that the ribosomal environment has on the strength of the base pairs
%U https://www.cell.com/biophysj/fulltext/S0006-3495(18)33231-4