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.

The effect of incomplete translocation can be understood in two ways. Incomplete translocation at the pre-translocational ribosome aligning with deX XXY produced more FS m (Pathway I), consistent with the model by Leger et al. (22) . Incomplete translocation at the pre-translocational ribosome aligning with XXY YYZ resulted in more FS z (Pathway III), consistent with the models proposed by Weiss et al. (23) and Namy et al. (24) . Enhancing incomplete translocation in Pathway I promoted an increase in the fraction of FS m among total frameshift proteins. On the other hand, enhancing incomplete translocation in Pathway III decrease the fraction of FS m . While these two pathways were supported by previous studies, the direct observation of FS m for HIV-1 and HTLV-1 pro-pol frameshift sequences provided proof for the validity of Pathway I. Interestingly, altering the extended frameshift sequence resulted in a significant change in frameshift protein compositions, supporting the role of the sequence upstream of the traditional slippery site XXY YYZ.