HIV-1 frameshift efficiency is primarily determined by the stability of base pairs positioned at the mRNA entrance channel of the ribosome

Mouzakis, Kathryn D.; Lang, Andrew L.; Vander Meulen, Kirk A.; Easterday, Preston D.; Butcher, Samuel E.

Multiple models have been proposed to explain the frameshift mechanism (1, 6, (31) (32) (33) (34) (35) (36) (37) (38) . Common among them are the following steps: (i) during translation, the ribosome pauses when the slippery sequence (UUU UUA in the 0 frame) is engaged in the ribosomal A-and P-sites (4, 18, 22, 39) . The pause is triggered by the downstream structure's resistance to unwinding. (ii) While paused, $5% of ribosomes slip 1 nt in the 5 0 -direction and continue elongation in the À1 reading frame. The proposed models are differentiated by the exact step at which the frameshift occurs: during aminoacylated-tRNA accommodation (31) , after accommodation, but before peptidyl transfer (1), after large subunit translocation (5) or after peptidyl transfer due to an incomplete translocation (37) . Alternatively, the 'many pathways model' of À1 PRF suggests that frameshift efficiency is the sum of frameshift events occurring, each of which could occur at these different points in elongation (36) .