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.

The minimal sequence for nearly, but not quite all, forms of −1 frameshifting is a tetranucleotide of the form Z ZZN and involves codon: anticodon dissociation and the anticodon re-pairing to mRNA at the overlapping −1 codon. Though noted as occurring at the sequence (G UU)A AAG where substitution of a C with the italicized A created a −1 shift site at which the frameshifting compensated for a nearby −1 frameshift mutation (393), A AAG frameshifting was first extensively studied (394) , and later systematically explored, with synthetic constructs (195) . Such −1 frameshifting occurs incidentally in Bacillus at A CGA AAG to give an extended cytidine deaminase (18) and at G CGA AAG is productively utilized by IS1222 to synthesize its transposase (189) , and with drugresistant mutant herpes viruses (6) . Studies with it showed that the efficiency of this type of relatively low level −1 frameshifting is dependent on the identity of the two flanking 5 bases. Studies in E. coli of these nucleotides in the sequence NNA AAG focused on the degree of anticodon loop flexibility and base 34 modification of the tRNAs decoding the 5 codon (an underscore separates the zero frame codons). Codons whose cognate tRNAs exhibited greater wobble propensity gave higher frameshifting levels probably due to increased liberation of the third codon base, A, for the re-pairing of tRNA Lys in the −1 frame (193) . E.