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.

A special circumstance is created when the intercodon is a stop codon at +1 or −1 frameshift sites, as occurs naturally in bacterial RF2 (+1 PRF), human antizyme (+1 PRF), Rous sarcoma virus (−1 PRF), and barley yellow dwarf virus (−1 PRF). For our studies a stop codon as the intercodon was artificially created for the HIV-1 site. In these cases, the decoding molecule is not a tRNA but a protein release factor, which, unlike a tRNA, does not interact solely with the triplet codon but also the downstream sequence of the mRNA [70] , [71] . Of interest is that the release factor has been shown to recognise disturbed stop codons in the A site of the bacterial ribosome [72] . Such an extended interaction between the release factor and mRNA:ribosome complex would be expected to compete strongly with frameshifting if the stop codon was occupying the ribosomal A site-more so than tRNA with the canonical mRNA:tRNA codon:anticodon interaction (and particularly if the intercodon is distorted in the A site). Consistent with this prediction, we found that the UGA suppressor tRNA was less able to prevent frameshifting than eRF1 at the HIV-1 site (Fig. 6C ). This effect would be predicted to depend upon the efficiency of decoding by the molecule during accommodation, after occupying the ribosomal decoding site, in addition to the concentration of the decoding molecule in the cell. In a distorted decoding site it is not easy to predict which decoding molecule (eRF1 or suppressor tRNA) would be the more efficient decoding molecule.