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.

The importance of the E site for frame maintenance has been established with bacterial ribosomes by analysis of the bacterial RF2 +1 frameshift mechanism that relies on destabilisation of E site tRNA binding [73] , and from the fact that weaker E site tRNA interactions (A•U rather than G•C) correlate with higher +1 PRF in E. coli [74] . Indeed, the E site plays a general role in frame maintenance in prokaryotic ribosomes [75] . Three 16S rRNA mutations located in helices 21 and 22 increase −1 PRF with the HIV-1 element [26] , and these are involved in E site tRNA binding. The model presented in Fig. 7 is consistent with these observations, although our experimental data are not directly informative in this regard. For HIV-1, slippage might occur first at the E site followed by slippage at the P site [26] , [76] , as opposed to the simultaneous-slippage model proposed originally [3] . Additionally, in yeast Bekaert and Roussel (2005) showed bioinformatically when X XXY YYZ is in the P and A ribosomal sites the two nucleotides immediately upstream in the E site are highly biased, suggesting an extended signal. In yeast, high frameshift efficiency corresponded to a pseudouridine at tRNA position 39 that might decrease stability of the P or E site tRNA interactions [77] .