The Highly Conserved Codon following the Slippery Sequence Supports -1 Frameshift Efficiency at the HIV-1 Frameshift Site

Mathew, Suneeth F.; Crowe-McAuliffe, Caillan; Graves, Ryan; Cardno, Tony S.; McKinney, Cushla; Poole, Elizabeth S.; Tate, Warren P.

The translation product resulting from frameshifting in HIV-1 Amino acid sequencing data have shown that the protein product of −1 frameshifting from the HIV-1 PRF element is heterogeneous, indicating the presence of multiple pathways leading to −1 PRF in HIV-1. The amino acid corresponding to the last codon of the slippery sequence (UUU, coding for phenylalanine in the −1 frame; or UUA, coding for leucine in the 0 frame) has been found to be 20-30% phenylalanine and 70-80% leucine in the protein product of −1 PRF [3] , [60] , [61] . Incorporation of phenylalanine (the minority product) in this position would occur before the intercodon reaches the A site if the ribosome frameshifts prior to peptidyl transfer, resulting in UUU occupying the A site and being decoded by tRNA Phe . This pathway has been described in detail by Liao et al. (2011) [60] . Incorporation of leucine, by contrast, could occur either before or while the intercodon occupies the A site [32] , [60] . A possible pathway for the latter scenario, in which leucine is incorporated into the peptide chain while the intercodon occupies the ribosomal A site, is described below.