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.

The observed frameshift efficiencies for the 3HJ WT and WT reporter constructs in RRL both fall within the range of previously measured frameshifting efficiencies for HIV-1 in vivo, which range from 2% to 5% (9, 15, 21, 24) . The wide range of observed frameshifting efficiencies in vivo is likely influenced by viral and cellular factors, for example, modulation of translation initiation by the HIV-1 TAR RNA structure (79) and polysome density (53) . We find that the conserved 3HJ secondary structure in the HIV-1 genomic RNA (54) causes a significant decrease in frameshift efficiency ( Figure 6 ). This observation is consistent with the previous hypothesis that the 3HJ secondary structure induces ribosomal pausing (54) . Pausing at the upstream secondary structure may promote stacking of consecutive ribosomes (80) , promoting a net decrease in frameshift efficiency because the mRNA would have less time to refold between ribosomes. Our data support this model and also indicate that local stability has a far greater impact on frameshift efficiency ( Figure 6 ).