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.

Limitation of a specific aminoacyl-tRNA can also occur in certain triplet repeat expansion situations. With disease level expansion of CAG repeats in huntingtin, frameshifting at multiple sites has been demonstrated, but in this case it is difficult to distinguish the relative effects of aminoacyl tRNA limitation from a stimulatory effect of a 3 structure formed from the repeat sequence (376) . This study importantly illustrates significance of relative expression levels of a relevant tRNA in different brain tissues. An independent study showed that mutation in a brain-specific tRNA causes neurodegeneration (428) . A subset of aminoacyl-tRNAs are tightly associated with translating ribosomes (429, 430) . To what, if any, extent this is relevant to CAG repeat, and other, frameshifting, is unknown. The issue is to what extent localized aminoacylation limitation for a ribosome translating, for instance a run of repeat codons, is a reflection of overall cellular limitation for that aminoacyl tRNA. In addition to extreme situations, such as when silk fibroin is being synthesized in silk glands, the pool of aminoacyl tRNA isoacceptors changes when different classes of mammalian mRNAs are being translated (431) . However, for the only virus tested where frameshift utilization is known, influenza A virus, it is the particular relevant local pool of isoacceptors that is selected rather than the tRNAs overall being adjusted (432) . Though some viruses encode their own tRNAs, whether any are relevant to frameshifting is unknown.