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.

A counterpart to targeting frameshifting with therapeutic intervention is the use of agents such as antibiotics for their crucial antibacterial effects, but which can have low-level effects on frameshifting even with mammalian ribosomes. While the large battery of proteases would rapidly destroy most proteins, this may not apply to all whether abberant or normally utilized, with potentially significant effects in special cases perhaps even for neurodegenerative disease (369) . Treatment of Clostridium perfringens infected horses with gentamycin or streptomycin caused in-frame restorative frameshifting in the decoding of a cryptic gene whose product is involved in the synthesis of a toxin that causes more accentuated and fatal progression of equine typhlocolitis (694) . At a substantial majority of frameshift sites, streptomycin does not cause detectable frameshifting, but at some it does (671) and is not surprising (369), due to aminoglycosides causing increased acceptance of near-cognate aminoacyl-tRNA and reduced acceptance time (402, 695) . However, even gentamycin and paromomycin which in general are more effective than streptomycin, commonly cause only very modest increases in frameshifting (696) . The oxazolidinones, linezolid and especially R chi-01 promote more but still often modest levels of frameshifting (696, 697) .