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.

This section on shift sites will conclude with the autoregulatory frameshifting in bacterial release factor 2 synthesis. The highly conserved shift site is CUU U, even though re-pairing to mRNA in the +1 frame involves first position G:U pairing. Other shift sites have doubtless been sampled repeatedly over the course of evolution, and UUU U does occur in a small minority of species. Significantly, in the release factor 2 genes that do not utilize frameshifting in their expression, the first position of the codon corresponding to the CUU is not conserved (443) . The most extensive substitution analysis of the CUU shift site, 32 variants, was performed with the 3 adjacent codon being UAG rather than UGA (390), though the values for the 6 substitutions that are the same as those used in an earlier smaller study with UGA (54), are consistent. CUU U was found to be by far the most efficient shift site raising the possibility that the simple, m1G, modification of the anticodon base 3 adjacent to that in the cognate tRNA Leu that pairs with the first codon base C, is important for the much higher levels than with UUU U where the counterpart base 37 of the cognate tRNA has the bulky adduct threonine in carbamoyl linkage to the 6-amino group of A37 (390) . While elaborate modification of base 37 of tRNA Phe helps restrain first position wobble in standard decoding, and first position wobble would not be relevant with a UUU U shift site, nevertheless its presence may be inhibitory for frameshifting. Several studies, including (354) , have shown that the identity of the base 3 adjacent to the ORF1 stop codon UGA is also very important, and a C at this position is highly conserved.