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.

In contrast to results presented in Fig. 5E , Kobayashi et al. (2010) reported that eRF1 is a general effector of −1 PRF frameshifting in HIV-1 when the intercodon is the natural GGG [55] . Although we did not observe this effect when eRF1 was over-expressed, given our uninterpretable results from depleting eRF1 we used suppressor tRNAs as an alternative decoding molecule of stop signals. Near-cognate tRNAs are naturally occurring potential suppressors of stop signals. They interact with termination codons by forming one or two base pairs with their anticodons but compete poorly with all but the weakest of stop signals. Artificially constructed cognate suppressor tRNAs that can form three Watson-Crick codon:anticodon interactions are highly competitive with eRF1 for decoding stop signals. If the changes in −1 PRF efficiency observed in Fig. 5E were mediated by a more general but unexplained property of eRF1, we would not expect to observe changes when using suppressor tRNAs. By contrast, if suppressor tRNAs modulated −1 PRF efficiency, then competition must be occurring between the suppressor tRNA and the endogenous eRF1 at the UGA intercodon within the ribosomal A site.