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.

Frameshifting near the end of an ORF encoding a structural protein to yield a fusion with an enzyme required in lower quatities, is typically at a low level as illustrated by HIV GagPol. In such cases, the potential for mutationally switching the downstream ORF to the zero frame cannot be simply accomplished, with retention of frameshifting for expression. However, it can occur with utilization of a different type of recoding. With a different retrovirus, Moloney murine leukemia virus, the downstream pol ORF is accessed by a few per cent of ribosomes reading through the gag terminator with near-cognate decoding of the stop codon. While some retroviruses utilize just a single such −1 ribosomal frameshift, certain others utilize two −1 frameshift events (62) and in these the first one is more efficient. At least two frameshifts occur in the decoding of one Euplotes gene (32, 63) , one mitochondrial gene has 10 (64) and the current champion gene which involves 12 reading frame shifts is also mitochondrial (56, 65) .