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.

Potyviruses may cause more than 30% of all plant losses due to viruses and cause immense monetary loss and wasted fuel in intensive agriculture, a figure of $20 billion per annum has been cited (168) . Regardless of the monetary figures, they cause severe hardship and starvation for many on subsistence agriculture. In contrast, a potyvirus caused the highly prized pattern on tulips that triggered the first economic boom bust 'mania' in Europe (in the 1600s), and tests for potyviruses in orchids are lucrative ( Figure 5 ). Until recently the small single-stranded RNA genome was though to have a single ORF that encodes a polyprotein which is cleaved to yield functional proteins. However, there is a short overlapping ORF, pipo, that is decoded as the Cterminal end of a fusion protein P3N-PIPO (169) which mediates virus movement in plants (168, 170) and is relevant to overcoming host resistance (171) and jumps in plant host range (172) . Though it was initially suspected that PIPO coding sequence was accessed by ribosomal frameshifting, it is instead specific viral polymerase slippage, with insertion of a single additional base relative to the template, followed by standard translation, that yields the additional product (42) (43) (44) . Irrespective of the outcome of future work to determine whether the slippage events occur during synthesis of the minus-strand replicative intermediate or the plusstrand progeny genome, the mRNA with the single extra base behaves as a novel sort of sub-genomic (actually, supergenomic) RNA. The requirement for synthesis of a complete polyprotein to confer cis-replication competence (173) has been suggested to mean that the RNA from which PIPO is translated, is not amplified (42) . With turnip mosaic virus, the amount of deletional or +2 slippage, was very low so the amount of expression from the +1 frame was very small. However, with clover yellow vein virus, a product with its C-terminal 5AA encoded from the +1 frame, and derived from transcriptional slippage at the same site, has been detected, and shown, like P3N-PIPO, to function in cell-tocell movement (174) (Figure 5B ). Four related potyviruses infecting sweet potato utilize an additional slippage site at a different location to permit access to a second overlapping ORF and synthesis of a 'transframe' product that uniquely inhibits short-distance movement of an RNA silencing signal (175, 176) .