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.

Significant frameshifting generally occurs at a discrete site, though when occurring at multiple repeat codons as in the decoding of huntingtin, multiple sites are involved (376) . Site-specific mRNA pseudouridylation occurs and is regulated by environmental conditions such as nutrient status (386) with AG decoding being distinctive (387) . Further, hydroxymethylcytosine performs an essential role in Drosophila brain mRNA (388) and there have been numerous studies on N 6 -methyladenosine in mRNA (389) . However, it is unknown if any utilized frameshifting occurs at an mRNA modification site, or is dependent on ribosome heterogeneity. Frame transitions generally involve realignment. Sites at which ribosomal frameshifting occurs exhibit considerable variation in their inherent 'shiftiness'. Many studies have shown that one relevant feature for the great majority of 1 or 2 nt ribosomal frameshifting is the balance between propensity for anticodon:codon dissociation and potential for re-pairing to mRNA at an overlapping codon in a new frame with tRNA modifications being relevant (54, 324, (390) (391) (392) , as described for one in detail at the end of this section.