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.

Frameshifting selected due to productive utilization of its derived protein product generally results in a proportion of ribosomes terminating on sequence on which ribosomes in another frame are continuing downstream translation. To an unknown extent, selection has presumably operated to generate features for avoidance of mRNA instability associated with the terminator in either of the utilized frames that is closest to the start codon. Avoidance is likely most relevant when the great majority of ribosomes are in the frame that leads to termination at the first terminator in either frame. Given the complexity of mRNA degradation and difference between the major classes of organisms, there is probably a diversity of answers with cytoplasmic transcription for many RNA viruses also being relevant. Parallels to the diversity of stabilities of internal UGA-containing selenoprotein mRNAs may emerge. However, attention is drawn to a sequence shortly after a frameshift site and 3 adjacent to a relevant stop codon, that binds a polypyrimidine tract binding protein that competes with UPF1 (20,21), a component of the nonsense mediated decay system. A more questionably relevant case involves the very different organization of an RNA virus genome whose decoding involves shifts into both alternative frames (22,23).