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.

With some analogy to the spread of viruses, transcellular propagation of protein pathogens was thought in mammals to be restricted to such diseases as Creutzfeldt-Jakob, scrapie and bovine spongiform encephalopathy (BSE). However, it has recently been realized that the amyloid assemblies of A␤ peptides and of tau proteins in Alzheime'rs disease and the ␣ synuclein assemblies in Parkinson's stochastically spread in a prion-like manner (365) . A small proportion of Alzheimer's disease is inherited and due to mutations in the gene encoding amyloid precursor protein. A small proportion of it is encoded transframe with respect to its DNA sequence (366) . Further, in both Alzheimer's and Spinocerebellar ataxia 3, after formation of intranuclear aggregates, some ubiquitin B has C-terminal Gly replaced by a Tyr followed by a 19-AA extension encoded trans-frame with respect to the DNA (366, 367) . This aberrant ubiquitin triggers neuronal apoptosis and mitochondrial impairment that likely contributes to at least Alzheimer's progression (368) . Though called UBB +1 in the publications just cited, in the notation generally used, including here, the C-terminal extension comes from the −1 frame (369) . Though the trans-frame encoded protein is being studied intensively, the nature of the event involved in its generation needs further investigation (369, 370) .