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.

Nucleic Acids Research, 2016, Vol. 44, No. 15 7045 For the luteovirus, barley yellow dwarf virus, a 6-nt internal loop on the 3 side of a stem loop 6 nt 3 of the shift site pairs with the apical loop of a stem loop 4 kb 3 of the shift site (110, 552, 553) . A similar arrangement, involving what is termed an ALIL pseudoknot, was also predicted for viruses in two Tombusviridae genera, Dianthovirus and Umbravirus (406, 463) . This was experimentally demonstrated for a member of each, red clover necrotic mosaic virus (554) and the RNA 2 (406) of pea enation mosaic virus (whose taxonomically unrelated RNA 1 is dealt with below). For RNA 2, the long-distance interaction modifies the lower stem of the stimulatory structure close 3 to the shift site, perhaps by strengthening its stability. However, the same study left open possible relevance of the interaction bringing close other sequence near the 3 end (406) . It is unknown if it is relevant that RNA 2, like the RNAs of many positivestrand RNA viruses, lacks a 5 cap structure and its capindependent translation features a sequence in the 3 UTR binding eIF4E and so recruiting eIF4F to mediate initiation via a long distance interaction (555) . (In barley yellow dwarf virus, the distal apical loop involved in long distance pairing to the frameshift stimulatory structure just 3 of the shift site is about 200 nts 3 of the element that permits cap-independent initiation.) Regardless, quite different considerations apply for the structure involved in bacterial IS3411 ribosomal frameshifting, and at least 27 other IS elements (45) . The counterpart involves pairing of the apical loop of a similarly positioned stem 1 with an internal loop of a stem loop 2 that is positioned in the range of 44 to 104 nts 3 depending on the IS element (45) . Remarkably the second component can, to some extent, act in trans (45) . With only two variant types currently known, others remain to be found. In addition, some unrelated long range effects remain to be explained including for phage T7 gene 10 frameshifting, where a CCCC sequence in the transcription terminator over 200 nts 3 of the shift site is involved (397) .