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 our earlier studies with bacterial ribosomes and the slippery sequence of the HIV-1 group M frameshift element [22] , we replaced the natural GGG intercodon with a stop codon (as occurs for the intercodon in Rous sarcoma retroviral RNA) because at the time we had the capacity to express the test element in bacteria in vivo and over-express the decoding bacterial release factors (RF) [33] . The bacterial RF modulated frameshifting with codon specificity, implying that if slippage occurred during elongation it was when the intercodon was being decoded in the ribosomal A site. The −1 PRF constructs used in these studies however, lacked the downstream stem-loop and subsequent NMR structural studies of this secondary structural element suggested that the second and third nucleotides of the GGG intercodon are at the very start of a less stable lower region of an extended structure [18] , [19] .