Stimulation of stop codon readthrough: frequent presence of an extended 3' RNA structural element

Firth, Andrew E.; Wills, Norma M.; Gesteland, Raymond F.; Atkins, John F.

Several alphaviruses, including Sindbis virus (SINV), utilize RT of a UGA stop codon in their replicase gene (30, 31) . For SINV, primarily on the basis of in vitro translation studies, the only contextual feature reported to be important for RT was the identity of the cytidine nucleotide immediately 3 0 of the stop codon, directly analogous to the results of the early stop codon leakiness studies (32) . Similarly, in the tobraviruses (specifically tobacco rattle virus) and, by implication, the pecluvirus, furovirus and pomovirus replicase gene, and the furovirus CP-extension gene, it has been reported that RT of the UGA stop codon might depend on just the three 3 0 -adjacent nucleotides (33) . For these plant viruses, and alphaviruses that utilize RT, the consensus motif in wild-type (WT) viruses is UGA-CUA or UGA-CGG (34) . In contrast, for TMV (where the RT codon is UAG), plant tissue culture experiments showed that the 6 nt immediately 3 0 of the stop codon are relevant, with the consensus motif for efficient RT being UAG-CAR-YYA (35, 36) . The same motif is utilized by a number of other plant viruses, while the motif UAG-CAR-NBA stimulates RT in yeast (37) . In terms of 5 0 stimulatory motifs, adenines at the À1 and À2 nucleotide positions have been shown to positively modulate RT in yeast and are a feature common to many virus RT sites, notably in the tobamoviruses, poleroviruses and luteoviruses (38) .