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.

The opposite type of situation is where frameshifting is advantageous because it leads to mRNA decay. Numerous high level frameshifting candidates for this have been identified (24-26). Many are not phylogenetically conserved, making it difficult to assess overall significance especially as the situation is different from where selection acts via the protein product. However, in some cases experimental analysis has yielded provocative insights as, for instance with the human CCR5 cytokine receptor that acts as a HIV-1 co-receptor with implications for other cytokine receptor mRNAs, especially interleukin receptor subunit mRNAs (27, 28) . This particular example is present from humans to lemurs. As a counterpoint to consequences of termination by frameshifted ribosomes, there can be dramatic effects of not having any stop codon in the new frame, as illustrated by a viral case (6) . On bacterial mRNAs lacking stop codons, tmRNA-mediated shifting of translation onto its own internal sequence is associated with both mRNA degradation (29) as well as abberant protein destabilization. (Utilization of frameshifting to lead to the unwinding of stem loops to permit downstream initiation is dealt with below.)