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 initial proposal for heptanucleotide −1 frameshifting involved tRNAs in both the ribosomal P-and A-sites shifting simultaneously before the peptidyl transfer reaction (102) . However, it was quickly instead proposed that the shift occurs after peptidyl transfer and perhaps even during translocation (94) , and numerous proposals have since been advanced including sequential slippage. The greatest departure from the notion of simultaneous −1 shifting is that just peptidyl-tRNA is involved in the slippage process with the incoming aminoacyl tRNA having the opportunity to also pair in the −1 frame. Experimental evidence for this has been obtained with a variant of the E. coli dnaX −1 shift cassette (403) . However, discussion of the relationship of that study to other recent biophysical studies and their combined implication are delayed until after the description of stimulators below, since they are key to the non-canonical ribosome states critical for understanding what happens at the shift site.