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.

Continuing with gene 60 bypassing: The take-off codon is paired to peptidyl-tRNA at the start of bypassing and so is unavailable for intra-mRNA pairing. Later, together with its flanking sequence, it forms a functionally important stem loop, designated 'take-off stem loop' (160, 385) (Figure 11 ). Part of the sequence involved is 5 of the take-off site. The time, or times, at which formation of the take-off stem loop is important remains to be determined -it has recently been discussed in detail (451) . Sequence 5 of that which becomes involved in the 'take-off' stem can form an independent stem loop, designated 5' stem loop (485) . Evidence is accumulating that by the time the take-off codon has reached the ribosomal P-site, the 'top' 5 bp of that stem have already paired just outside the ribosomal mRNA exit channel. The current model is that after liberation of the mRNA on P-site codon: anticodon dissociation, completion of pairing with 4 additional base pairs in the 5 stem loop serves as a 'motor' by pulling mRNA 5 to start bypassing movement (451, 485) [Such mRNA structure formation mediated ribosome positioning has some parallels to the dicistrovirus InterGenic Region (IGR) IRES forming an extended structure that directs a proportion of the ribosomes on Israeli acute paralysis virus RNA to commence initiation in the +1 rather than the zero frame (181, 486, 487) .]