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.

Other factors can modulate the frameshift efficiency, such as translation initiation rates (37, 53) . Increased translation initiation rates lead to increased polysome density, which can cause ribosomes to stack at the frameshift site. This in turn affects the rate of mRNA refolding during translation and leads to a decrease in overall frameshift efficiency (37, 53) . Ribosome stacking can be promoted by RNA structure that precedes the frameshift site. Studies examining the secondary structure of the HIV-1 genomic RNA within capsids have revealed that the frameshift site is part of a conserved three-helix junction (3HJ) (54, 55) . It has been hypothesized that the role of this secondary structure is to decrease the rate of translation (54) , which may affect frameshifting by facilitating pausing and inducing ribosome stacking.