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.

To commemorate this year the 50th anniversary of the full-deciphering of the genetic code and the 100th anniversary of Crick's birth, we provide an overview of knowledge gained since then on the aspects of the dynamic nature of both mRNA generation and code readout gained by studying frameshifting, especially ribosomal frameshifting. For space reasons, other features of the 'extra layer' in code readout, including dynamic codon redefinition and other processes that yield a trans-frame encoded product with respect to the DNA will generally be omitted (even though Figure 1 . Genetic 'Bletchley-ism': As illustrated with three letter words, the framing of genetic informational readout can be modified to convey meaning from genetic 'hieroglyphs' (cryptography) or additional and hidden meaning (steganography). Embellishing the old adage 'From tapes to shapes' (proteins), in several cases this involves 'shapes-in-the-tapes' unlike counterparts in many human languages. The process is dynamic, and the competition yields products from both standard reading and frameshifted reading. The relative proportions of the products from each are case dependent. Examples of genetic cryptography involving translational bypassing are in the decoding of phage T4 gene 60 and the mitochondrial genome of the yeast Magnusiomyces capitatus (56, 65, 158) and another type is in decoding the mitochondrial genome of glass sponges (252) . The latter is a WT translation component counterpart of the suppression of frameshift mutants by suppressor mutants of translational components. Examples of genetic steganography involving transcriptional realignment are in the gene expression of paramyxoviruses, potyviruses and the bacterial insertion sequence Roseiflexus IS630 (42, 99, 617) ; examples of genetic steganography involving ribosomal frameshifting are in the decoding of influenza A virus expression (125, 270) and D. melanogaster APC (46) . While standard expression of most bacterial release factor 2 genes, and also probably eukaryotic antizyme genes except for antizyme 3, yields a product that is non-functional on its own, the +1 frameshifting required for productive expression has been positively selected. The representation was inspired in part by a genetic framing garden 'rebus' (812) , a slide by V.N. Gladyshev and a recent publication (1). certain RNA processing (2) involves a ribosome/nascent chain complex, indel editing can have similar consequences to RNA polymerase slippage, and of course splicing is of major importance). However, tmRNA which has been recently reviewed (3, 4) will be treated minimally.