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.

The regulatory frameshifting required for bacterial release factor 2 and eukaryotic antizyme synthesis has not been substituted in any known organism with regulatory dynamic stop codon redefinition (stop codon readthrough) involving ORF2 being in the same frame as ORF1. However, in a number of retroviruses, including Moloney murine leukemia virus (MuLV), GagPol is synthesized via in-frame readthrough of a UAG stop codon (92, 93) rather than via frameshifting. It uses a stimulatory pseudoknot that is only rather ineffectively substituted by its counterpart mouse mammary tumor virus frameshifting stimulatory pseudoknot even though they are similarly positioned 3 of the recoding sites (637) . Substituting instead the HIV frameshift stimulatory signals resulted in readthrough levels only 2-to 3-fold lower than WT (638) . Experiments with two plant viruses that utilize readthrough to express their RNA dependent RNA polymerase, showed that recoding signals of one of them, carnation Italian ringspot virus (genus Tombusvirus) was partially functional for stimulating frameshifting whereas that of the other, tobacco necrosis virus D (genus Betanecrovirus), was not (639) . The similar recoding signals are bipartite and analogous to frameshifting stimulatory counterparts in barley yellow dwarf virus (genus Luteovirus) (110) and red clover necrotic mosaic virus (genus Dianthovirus) (554) with the 4 kb distant pairing.