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.

Translation of only a short zero frame sequence can be adequate to permit the utilization of frameshifting that acts as a sensor and effector of a regulatory circuit. The frameshifting can result in zero frame product being fused to functionally important domains encoded by the new frame. With E. coli release factor 2 mRNA, the functionally important part of the product is synthesized from the new frame by frameshifted ribosomes (refs. below) . Though it has not been experimentally investigated, there may be counterpart Nucleic Acids Research, 2016, Vol. 44, No. 15 7011 −1 frameshifting early in the decoding of phage cI mR-NAs where it is the short frameshift product that is rapidly degraded and the act of its synthesis serving as a 'ribosome sink' (57) , perhaps analogous to that, probably for a different regulatory purpose, in decoding some cardioviruses (58, 59) . In contrast, the function of frameshifting can be unrelated to products of the overlapping ORFs on which the frameshifting occurs. Though long postulated (60) , a bacterial case has recently been discovered where translation of a short zero frame leads to ribosomes frameshifting and their continued progression in the new frame affecting significant mRNA structure. In this instance, the consequence is allowing initiation of synthesis of an important downstream encoded protein (61) .