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.

Productive frameshifting is generally in competition with standard decoding. At the functional level there are three broad classes. In many cases the proportion of ribosomes that shift frame, or of polymerases that slip with consequent frameshifting with respect to their template, is constant (though in some cases this may reflect our ignorance of a relevant regulatory condition). This is often termed 'set ratio' frameshifting and the function is commonly generation of an extra N-terminally coincident product. In a second class, frameshift efficiency is responsive to the level of initiation or a trans-acting factor. In this class the frameshifting acts as a sensor and effector for regulatory purposes, either via synthesis of a functional trans-frame encoded product, mRNA half-life or new frame ribosome movement affecting translation of a downstream ORF, e.g. by affecting mRNA structure and initiation site accessibility. A third functional class is 'corrective' frameshifting where the effects of a 'problem' indel, at the DNA level (or potentially at the mRNA level, e.g. U-indel editing) are translationally compensated. Most known occurrences of this class are in mitochondria.