The many paths to frameshifting: kinetic modelling and analysis of the effects of different elongation steps on programmed –1 ribosomal frameshifting

Liao, Pei-Yu; Choi, Yong Seok; Dinman, Jonathan D.; Lee, Kelvin H.

A mathematical framework developed upon the translation elongation cycle revealed three distinct kinetic pathways for À1 PRF. The model describes how alterations of these kinetic parameters can affect not only changes in frameshift efficiency, but also changes in the composition of frameshift products under different conditions. In addition, the model identifies the dominant parameters, representing steps in the translation elongation cycle, on À1 PRF. Experimentally targeting these steps resulted in different levels of frameshifting efficiency, consistent with model predictions. A mutation in the À1 frame E-site sequence was shown to dramatically change the composition of frameshift products, suggesting an important role for the sequence upstream of the slippery site. Our results suggest that not only the frameshift efficiency, but also the compositions of the frameshift products, are worth investigating to advance our knowledge of À1 PRF.