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.

It is difficult to predict what the ribosome complex might look like in these atypical states created by the unusual elements within the RNA at frameshift sites. For example, it has been reported recently that a prokaryotic −1 PRF-stimulating element, when positioned at the entrance channel of the E. coli ribosome, can trigger an unusual 'hyper-rotated' state [68] . The tRNA Gly interacting with the GGG intercodon may be distorted in the A site, essentially [26] , is positioned in the A site. The extended stem-loop is at the entrance to the ribosome, with the first nucleotide of the intercodon (orange) in the +13 position. B. The lower stem of the structure unwinds and allows the slippery sequence into the decoding centre. The stable upper stem-loop is positioned near the entry channel of the ribosome. Tension arising from resistance to unwinding may allow slippage from the A and P sites at this stage. C. After partial unwinding of the stable upper stem-loop, binding of tRNA Gly to the intercodon, perhaps in a distorted state, competes with −1 frameshifting. D. The tRNA Gly bound to the intercodon is decoded and translation proceeds in the 0 frame. This is the most common event, resulting in the translation of the Gag product. E. If the tRNA Gly is not decoded, −1 frameshifting by the E and P site tRNAs occurs to relieve tension on the mRNA, resulting in the translation of Gag-Pol. An incoming tRNA Arg is shown. unstable and poorly accommodated for peptide bond formation [32] . Consistent with this model, ribosomal mutations that increase the rate of accommodation negatively affect −1 PRF efficiency [67] .