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.

Many studies have used only modest-length sequence flanking the known or suspected, frameshift site and in some cases this led to misunderstanding. It has taken clever sleuthing to reveal the very important distant-acting features in luteoviral, HIV, herpes virus drug resistant mutants and S. cerevisiae antizyme frameshifting described above. In contrast, there has been general awareness of the need for caution in (i) extrapolating from in vitro to in vivo or when heterologous expression is involved and (ii) regarding E. coli growing in rich lab media as reflecting most bacterial growth in nature. Undue proximity to the initiation site for practical reasons in certain early studies was an issue, and issues relating to mRNA stability, ribosome spacing level and distinction between transcriptional and translational 'frameshifting' are also now more addressable.