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 this study, a mathematical framework was developed for À1 PRF. To our knowledge, this is the first kinetic model to explain the production of two types of À1 frameshift proteins through three distinct kinetic pathways. Using deX XXY YYZ fgh as an example, Pathway I predicts that a pre-translocational ribosome aligning with deX XXY may shift reading frame during incomplete translocation, producing the frameshift product (FS m ) incorporating a À1 frame aa-tRNA in the frameshift site (codon YYY). Additionally, Pathway II predicts that a ribosome can change reading frame due to simultaneous slippage of P-and A-site tRNAs for a ribosome aligning with XXY YYZ, generating a frameshift product (FS z ) incorporating the zero frame aa-tRNA in the frameshift site (codon YYZ). Lastly, in Pathway III, a pretranslocational ribosome aligning with XXY YYZ may also undergo incomplete translocation to generate FS z .