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.

In our earlier study, a kinetic model successfully described the effects of ribosome E-, P-and A-site interactions on +1 PRF (27) . A similar approach can be applied to understand the mechanism of À1 PRF. The mechanistic model in the present study proposes that À1 PRF can occur during translocation and/or aa-tRNA accommodation. Figure 1 describes the overall framework using abc deX XXY YYZ fgh sequence as an example, where spaces separate zero frame codons and the slippery sequence is underlined. When À1 PRF occurs during translocation, the presence of the downstream stimulatory structure forces the ribosome to translocate by two, rather than three, bases toward the 3 0 -end of the mRNA, thus shifting the reading frame. If this 'incomplete' translocation occurs to the pre-translocational ribosome aligning with deX XXY, translation of the À1 frame begins at YYY. Alternatively, if incomplete translocation occurs to the pre-translocational ribosome aligning with XXY YYZ, translation of the À1 frame starts at Zfg. When À1 PRF occurs during aa-tRNA accommodation, the two tRNAs interacting with XXY YYZ slip to base pair with XXX YYY. Consequently, translation of À1 frame starts at Zfg (Figure 1 ).