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.

With delayed or sub-maximal A-site pairing, and dissociation of at least peptidyl-tRNA pairing being important for, at a minimum, the majority of productive frameshifting cases, thoughts turn to the extremes of where either the frameshifting is completely non-cognate or where the mRNA slides freely. Non-cognate −1 frameshifting was shown in an early in vitro study that revealed frameshifting significance of the balance of tRNA. With an unperturbed balance of tRNAs, an ACC decoding tRNA Thr was shown to read a CCN proline codon to generate an elongated form of phage MS2 synthetase (73,75) (Figure 9 ). The identity of just 4 anticodon loop bases is important for this frameshifting (452) , but distinction between two alternative mechanisms remains unresolved (453) and whether there is relevance for other cases of frameshifting remains to be seen. [The only other tRNA found in that study to mediate non-cognate frameshifting was a tRNA Ser and it is these two tRNAs that decode AG codons (387, 454) .] The best known case of a different type of extreme recoding involving mRNA sliding, is in decoding phage T4 gene 60. Peptidyl-tRNA dissociates from codon 46, GGA and re-pairs to mRNA 47 nts 3 at GGA with coding resuming at the 3 adjacent UUA, codon 47. This and other cases involving stimulators are considered below. However, sliding on runs of A has recently been reported (384, 455) .