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.

So far the only evidence for this comes from a study of antizyme +1 frameshifting in the Agaricomycotina class of Basidiomycota fungi. A nascent peptide encoded between codons 14 and 4 5 of the shift site, UUU, is highly conserved at the protein identity specific level (270, 466) . It is an important stimulator and serves a polyamine-sensing role for modulating antizyme frameshifting levels and so for the autoregulatory circuit (466) . It is perhaps even likely that part of the mRNA encoding this nascent peptide signal also functions as a recoding signal at the mRNA level in the mRNA exit channel and while it appears that the identity of the nts immediately 5 of the shift site are important at the mRNA level, effects at the amino acid level may in addition be relevant (466) . The Agaricomycetes are the only examples so far where bioinformatic analysis has pointed to a nascent peptide stimulator. However, we consider it likely that rather than Agaricomycetes being exceptional in that respect they may instead be exceptional in having reduced, or no, importance for the nucleotide sequence encoding a nascent peptide stimulator also having an important stimulatory role at the level of mRNA in the ribosomal mRNA channel. In this hypothesis, the counterpart nascent peptide sequence is also important in higher eukaryotes, but it is not apparent bioinformatically due to lack of third codon position variation because of the stimulatory action at the mRNA level also. Despite no pause being evident just 5 of the shift site at the end of ORF1 in ribosome profiling experiments, perhaps because of sensitivity reasons, the hypothesis raises the issue whether prolines and glycines are encoded in a relevant position upstream of the antizyme frameshift site. Some interchangeability between the imino acid proline which is very different from glycine could be informative in relation to the distinction between potential nascent peptide decoding effects and those due to either product function outside the ribosome or nucleotide sequence effects during decoding.