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.

Before the recent application of relatively new biophysical techniques, including that used to identify the progressive slowing over several codons discussed in the nascent peptide section, there were many studies on pausing and emerging results from ribosome profiling are highly relevant. Frameshift generated IS911 transposase activity is ∼200-fold higher when it acts in cis than when supplied in trans. Pausing associated with the frameshifting influences cis preference presumably by facilitating sequential folding and cotranslational binding of the transposase (190) . This in turn influences the (cis) preference for transposase to act directly on the IS element that encoded it rather than on other copies of the same element (190) . Selective rational is provided by cells potentially having many copies of IS elements, and the need to tightly control transposition. Despite the elegance of this example, early pausing studies proved difficult. For a long time, some considered pausing as the key feature of programmed frameshifting with the nature of the shift site being the main determinant of the outcome of the non-standard event facilitated by the stall. Others hoped that the study of stimulators was not merely a study of different ways to induce a pause, with considerations of potential susceptibility to vacant A-site specific nuclease and tmRNA etc (see the 3rd next paragraph).