Antisense-induced ribosomal frameshifting

Henderson, Clark M.; Anderson, Christine B.; Howard, Michael T.

Structural studies indicating that the mRNA begins to enter the ribosome 7-9 nt downstream from the A-site codon is of direct relevance to this study (50, 51) . Our results indicate that maximal frameshifting is induced when the antisense-mRNA duplex begins 3 nt downstream of the UGA of the shift site, in agreement with the distance found between the UGA of the shift site and the beginning of stem 1 of the pseudoknot stimulator found in antizyme genes. Given this distance, the implication is that the stimulatory secondary structure would be encountered by the ribosome when the UCC codon enters the A-site of the ribosome. Perhaps as suggested by the structural studies of the IBV-1 frameshift inducing pseudoknot, the codon-anticodon interactions between the UCC codon and Ser-tRNA Ser are disrupted during translocation to the P-site. Given the importance of the UGA codon during frameshifting at the UCC UGA shift site, subsequent events following translocation of the UCC codon to the P-site and UGA to the A-site must influence frameshifting efficiency. This latter event most probably involves competition between termination and +1 frame decoding when the UGA codon is in the A-site. Various discussions have been presented for the importance of A-site and P-site events during ribosomal frameshifting (7, 52) and clearly, further investigations of this topic are warranted.