A dynamical model of programmed -1 ribosomal frameshifting.

Programmed -1 ribosomal frameshifting is the most widely used translational recoding mechanism of RNA viruses. How the frameshifting occurs at the slippery sequence on the presence of a downstream mRNA pseudoknot has not been fully understood. Here, we present systematical analysis of the -1 frameshifting that can occur during every transition step in elongation phase of protein synthesis by Escherichia coli ribosomes, showing that the -1 frameshifting can occur mainly during three periods. One is during translocation step, another period is after the posttranslocation and before the binding of the ternary complex aminoacyl-tRNA.EF-Tu.GTP, and the third period is after codon recognition and before peptidyl transfer. Of the three periods, the translocation step makes the most contribution to the -1 frameshifting. During the translocation step when the mRNA channel is open, due to the presence of energy barrier to the forward translocation of the ribosome along the mRNA template, which results from unwinding of the mRNA pseudoknot, the reverse ribosomal rotation from ratcheted to non-ratcheted conformation induces the frameshifting and futile translocation besides the effective forward translocation. During the other two slow periods when the mRNA channel is tight, the annealing of the unwound base pair in the mRNA pseudoknot can also promote the -1 frameshifting. Our theoretical results provide a consistent explanation of a lot of independent experimental data and also provide predicted results.