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 UGA cognate suppressor was competitive with eRF1 at the +1 antizyme frameshift site and reduced frameshift efficiency from 25% to 10% (P < 0.01), in contrast to the UAG noncognate suppressor that produced no significant change (Fig. 6B) . When either of the vectors encoding UAG or UGA suppressors or control tRNAs were co-expressed with the HIV-1 element containing the GGG codon, there were no statistically significant changes in −1 PRF efficiency (UAG suppressor) or no effect (UGA suppressor; Fig. 6C left) . By contrast, with UGA or UAG as the intercodon, frameshift efficiency increased and with expected cognate specificity. Fig. 6C (right) shows an example with UGA and UAG suppressors and with the UGA PRF element but with 'repair' of the stem-loop (see Fig. 2 ) to correct the disruption at the bottom of the loop. These data reinforce the conclusion that the intercodon of the HIV-1 element is available in the vicinity of the A site for decoding by a tRNA or by a protein release factor before frameshifting occurs.