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.

Depending on the realignment possibilities present, ribosomal frameshifting can be prone to occur when the Asite codon is slow-to-decode, due to limitation of the relevant aminoacyl-tRNA. Arising from his group's studies of amino acid starvation on single-nucleotide frameshifting (407) (408) (409) , Jon Gallant referred to such codons as 'hungry' codons. A slow-to-decode A-site is more generally important for +1 frameshifting than it is for −1 frameshifting. A very interesting occurrence involves the expression of Ty elements in S. cerevisiae and related yeasts. The Ty1 shift site, CUU AGG C on its own mediates a remarkable 40% +1 frameshifting. The S. cerevisiae shift site for ABP140 is identical and that for EST3 (CUU AGU U) is similar. The anticodon of the tRNA Leu that decodes CUU in the Ty1 shift site is 3 GAU 5 which has its wobble base 34, U, unmodified. This allows the tRNA in vivo to read all 4 CUN codons including CUU (410) . Where U:U apposition is involved, it is akin to the 2-out-of-3 reading identified elsewhere (411, 412) . Poor zero-frame codon pairing by peptidyl-tRNA Leu facilitates dissociation permitting re-pairing to mRNA at the overlapping +1 frame UUA. Slow recognition of A-site AGG by low abundance cognate tRNA Arg (anticodon 3 UCC 5 ) facilitates the frameshifting (209, 210) . The high abundance of tRNA Gly (anticodon 3 CCI 5 ) (413) cognate for the overlapping Ty1 +1 frame codon, GGC, is also important for efficient frameshifting. The implied competition for A-site decoding is mechanistically informative (414) .