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.

One of the early discoveries of viral frameshifting was the low level −1 frameshifting utilized by the double-stranded DNA tailed phage to link the synthesis of two products whose molar ratio of 30:1 is crucial for tail assembly (36, 40, 41) . Neither product is present in the mature virions. The product of standard translation gpG, and the corresponding part of the longer and frameshift-derived gpGT product bind to the tail length measure protein, to form a complex with many molecules of gpG per single molecule of gpGT. The −1 frame encoded T domain binds to the major tail shaft subunit and may recruit it to polymerize around the tape measure protein which then determines its length (41) ∼192 copies of the major tail subunit protein are in the final structure ( Figure 4) . This low-level 'G-T' frameshifting is widely conserved among other long tailed dsDNA phages, except T4, despite low sequence similarity of the respective ORFs of the different phages. However, in P2 and related phages the frameshift efficiency is 2-to 3-fold higher (141) . Counterpart −1 frameshifting also appears to be utilized by the siphoviruses Haloarcula vallismortis tailed virus 1 (HVTV-1) and three Haloarcula californiae viruses (HCTV-1, 2 and 5) that infect halophilic archaea, though that used by the myovirus Halorubrum sodomense tailed virus 2 (HSTV-2) is very likely +1 frameshifting (48, 49) . Encoding length regulators is not unique to viruses, bacteria encode an analogous molecular ruler. One class is the Type III secretion systems -the use of transcriptional slippage in expression of several of these is described below.