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.

Bacterial IS elements are small, 800-2700 bp, transposable elements. Sometimes they are present in only one or a few copies per bacterium, but up to more than a thousand in some cyanobacteria (182) . The over 4000 known different IS elements have been classified into several families (183) . While use of a frameshift event occurs in the decoding of the IS1 (184), IS3 (185, 186) , IS5 and IS630 families, it is very common in the IS3 family, which comprises 27% of the known IS elements (187) . Frameshifting serves to fuse the product of an upstream ORF, which generally encodes a DNA-binding protein that can on its own, act as a regulator, with a catalytic domain encoded by a partially overlapping downstream ORF that is often in the −1 frame ( Figure Figure 6 . Bacterial Insertion Sequence (IS) with two partially overlapping ORFs. Many IS elements have this type of gene organization. Utilization of ribosomal frameshifting to allow a proportion of ribosomes translating orfA to access orfB has been studied in depth in a variety of IS elements, but transcriptional slippage is now known to be used as an alternative by a substantial number of IS elements. 6 ). The fusion has the transposase activity. Where tested, the level of frameshifting was found to determine the level of transposition (188, 189) . As a low level of transposase is optimal to minimize insertion-mediated host gene disruption, the frameshifting level is generally low. This mostly affects transposition frequency of the same IS element rather than copies of the same element located elsewhere on the chromosome, since transposase has a strong cis preference. This is related to the frameshifting itself since an associated pause signal influences cis preference presumably by facilitating sequential folding and cotranslational binding of the transposase (190, 191) .