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.

There is also a third mammalian antizyme, antizyme 3, and it is restricted to developing male germ cells (298, 299) . In contrast antizymes 1 and 2 are expressed in nearly all other cells where the requirement for polyamines may be lower. Functioning antizyme 3 is required for the rigid connection of sperm heads to tails and so for male fertility (300, 301) . A substantial proportion of the translation initiation on antizyme 3 mRNA is at an in-frame CUG codon further 5 with respect to the frameshift site than the AUG initiators for antizymes 1, 2 or 3, and so the product is Nterminally extended (301) . Frequent termination at the stop codon 3 adjacent to the frameshift sites can result in synthesis of the ORF1 product, p12, that has a distinct separate activity. p12 interacts with myosin phosphatase targeting subunit 3 (MYPT3), a regulator of protein phosphatase 1␤, and affects phosphatase activity (301) . Expression of full-length antizyme 3 is very low, and at least in heterologous tissue culture cells the frameshifting efficiency is also very low (266) . In marked contrast to antizymes 1 and 2, at what is expected to be standard expression levels, antizyme 3 has a stabilizing effect on it, probably by antagonizing antizyme inhibitor. Instead of targeting ornithine decarboxylase for degradation, antizyme 3 may serve to reversibly 'store' ornithine decarboxylase monomers (302) . This mechanism would allow a much faster restoration of ornithine decarboxylase activity than any mechanism mediated by antizymes 1 or 2, as they require de novo synthesis of the protein (302) .