Ribosomal frameshifting and transcriptional slippage: From genetic steganography and cryptography to adventitious use

Atkins, John F.; Loughran, Gary; Bhatt, Pramod R.; Firth, Andrew E.; Baranov, Pavel V.

As described above, the influenza A virus minimal frameshift cassette, UCC UUU CGU has been used to tentatively identify the shift site of previously identified occurrences of viral frameshifting where the precise location and identity of the shift sites involved was obscure. Utilization for searches of cellular gene utilized frameshifting is also possible (125) . Mutating the UCC codon to AGC (serine) or to GGG, CCC or AAA resulted in a 40 to 70% reduction in the frameshifting efficiency (39), giving credence to the possibility that UCC plays an important positive role in the E-site or at least 5 of the codon to which peptidyl-tRNA is paired at commencement of the shift (125) . Though it is somewhat of a 'special' case because of the nature of its stimulatory element (see below), prior work on E. coli release factor 2 frameshifting lead to the proposal that weaker 'E-site' pairing disturbance favored higher +1 frameshifting levels (443) (444) (445) (446) . However, though likely different for −1 frameshifting, E-site relevance was also demonstrated for HIV (405, 447, 448) , pea enation mosaic virus (406) and other cases of frameshifting. Additionally, in yeast, bioinformatic evidence suggests that when X XXY YYZ is in the P and A ribosomal sites, the identity of the two nucleotides immediately upstream in the E site are highly biased, suggesting an extended signal (449) . Fluorescence and FRET studies either involving single ribosomes or ensemble approaches with the stopped-flow technique showed that Esite dissociation is delayed on ribosomes stalled by the E. coli dnaX-, or a coronaviral, 3 −1 frameshift stimulatory el-ement (403, 450) . Nevertheless, single molecule studies with zero-mode waveguide tracking of ribosomes show that the E-site tRNA is released before the ribosome rotates backward, both with E. coli dnaX −1 frameshifting and especially with T4 gene 60 bypassing (403, 451) .