Molecular model of ribosome frameshifting.

Normal tRNAs can cause two- and four-base translocation errors by mistranslating certain noncognate codons. Several cases have been reported that reveal the identities of the frameshift-provoking tRNAs--i.e., the shifty tRNAs--and the mRNA sequence encompassing the site of frameshifting--i.e., the shifty codons. Here, a striking uniformity between the anticodon loops of the shifty tRNAs and their shifty codons is described. Stable "offset" anti-codon X codon pairs are postulated for each of the shifty tRNA-shifty codon combinations. This offset anticodon X codon pair leads to two- and four-base translocations when viewed in terms of the reciprocating ratchet mechanism of translocation.