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.

We propose a modified model of HIV-1 frameshifting to accommodate a role for the intercodon in slippage. This is nonetheless consistent with existing models of −1 PRF, where tension created by opposing forces of forward translocation and resistance to unwinding of the stemloop is a crucial determinant of frameshift efficiency (Fig. 7 ) [62] [63] [64] . mRNA enters the ribosome 13±2 nucleotides from the first (+1) nucleotide of the P site codon [63] , [65] , [66] . In this scenario, the GGG intercodon would be positioned at the entrance to the mRNA channel when the first nucleotide of the slippery sequence has just entered the A site (Fig. 7A) . Indeed, the distance between the slippery sequence and the structural element has been implicated as contributing to frameshifting [23] , [64] .