HIV-1 frameshift efficiency is primarily determined by the stability of base pairs positioned at the mRNA entrance channel of the ribosome

Mouzakis, Kathryn D.; Lang, Andrew L.; Vander Meulen, Kirk A.; Easterday, Preston D.; Butcher, Samuel E.

The HIV-1 frameshift site is composed of a heptanucleotide slippery sequence (UUUUUUA) followed by a downstream RNA stem-loop ( Figure 1A ). The slippery sequence follows a general XXXYYYZ consensus sequence, where X can be any nucleotide (nt) type, Y can be A or U and Z is not G in eukaryotes (15, 18) . This sequence allows near-cognate and cognate re-pairing of the A-and P-site tRNA anticodons, respectively, in the À1 reading frame. HIV-1's slippery sequence is especially 'slippery', and in the absence of a downstream structure increases the basal level of ribosomal frameshifting from $0.0001% to 0.1% per codon (9, 19, 20) . However, in order to further stimulate frameshifting to the levels required for viral replication, the slippery site must be followed by a stable RNA structure (9, (21) (22) (23) (24) (25) (26) (27) (28) (29) (30) (Figure 1A) . Thus, frameshifting is achieved by the cis coupling of the slippery site and downstream structure (1, (9) (10) (11) 21) .