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 second round of frameshifting, occurring as the intercodon occupies the A site and the stable upper stem-loop resides at the beginning of the mRNA entry tunnel, then would be facilitated by a partially distorted intercodon and may be thought of as a competition between conventional decoding and frameshifting (Fig. 7D and Fig. 7E ). Different tRNAs, with their unique primary structures, modifications, and cellular concentrations would be predicted to have different binding capabilities to a distorted A site codon (as in Fig. 7C ). Consistent with this prediction, we observed a variation in frameshift efficiency among different intercodons decoded by different tRNAs (Fig. 3) . UGG (tRNA Trp ) was less capable, and AGG and CGG (tRNA Arg ) more capable of maintaining the reading frame compared with GGG (tRNA Gly ). A third base A (GGA, AGA and CGA intercodons) all produced significantly lower levels of frameshifting (i.e. better frame maintenance) than their third-base G counterparts, perhaps because A•U wobble-base pairing is stronger than G•U. Alternatively, the ribosome may undergo an incomplete translocation at this stage, resulting in elongation continuing in the −1 reading frame [31] . In a +1-frameshifting system, out-of-frame tRNAs are capable of influencing frameshifting, indicating substantial plasticity of the ribosome in these unusual circumstances [69] .