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 protein products of the paraneoplastic mammalian antigen-like genes PNMA3 and PNMA5 (Ma3 and Ma5) genes are targets of an autoimmune response triggered by the ectopic expression of antigens in tumor cells (225) . The effects of the indirect autoimmune response are frequently detectable before the tumor or its direct consequences. In contrast to Ma3 the evolutionary distance between Ma5 orthologs from mouse and human is far longer. Ma5 is not expressed in mouse brains and its expression in primate neocortex is highly restricted to a specific layer of an association area unlike Ma3 (226) . Ma3 expression involves ca. 20% efficient −1 frameshifting at a classical heptanucletide shift site stimulated by a classical H-type pseudoknot, and though not analyzed in detail, Ma5 appears similar (227) . The product of the sequence accessed by frameshifting is not similar to any known protein (neither Ma3 nor Ma5 encode any Pol domain). PNMA evolution in marsupials has yielded significantly different PNMA genes (228) .