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.

Efficient bypassing of 50 non-coding nucleotides in decoding phage T4 gene 60, is very dependent on a nascent peptide stimulator (160) that promotes the codon:anticodon dissociation that is a prelude to mRNA sliding during bypassing (451, 483, 484) , and also affects the fidelity of coding resumption (483) . The nascent peptide recoding signal causes progressively slower translation of the last five codons before the site in gene 60 mRNA of codon:anticodon dissociation. The bypassing step takes 10 to 20 times longer than a standard cycle step, and after coding resumption in the new frame, step times take several cycles to return to normal. The initial progressive slowing is very important for ribosomes assuming the noncanonical rotated state that is central to bypassing (451) . Such progressive slowing is distinct from the prior prevailing thought that pausing sites in general would be single discreet sites. Unlike its secM counterpart the most important part of the gene 60 nascent peptide signal, KKYK, is 25 amino acids from the P-site when its effects on translational slowing starts to become apparent and 30 amino acids from the P-site at the time of codon:anticodon dissociation (451) . Consistent with the number of amino acids from a key part of the nascent peptide signal to the P-site being important, while retaining the 14 gene 60 codons closest 5 to the codon: anticodon site, replacing the further 5 codons with secM sequence natively just 5 of their pause site, still resulted in significant bypassing (451)