In contrast to EST2, the TBF1 signal promoted $5% frameshifting (15), but is not predicted to be highly stable (À9.5 kcal/mol). Thus, all of its mRNA destabilization activity was through NMD (compare Figure 2B with C). The thermodynamic stability of the BUB3 signal is predicted to have an intermediate value to EST2 and TBF1 ($À12 kcal/mol), and hence the potential contribution of NGD to the stability of its reporter was significant. Interestingly, this signal only promoted $1% frameshifting (15) , yet the contribution of NMD to its destabilization was greater than observed for TBF1. One possible explanation for this apparent discrepancy may stem from the fact that, in order to measure frameshifting, one base had to be deleted from the spacer region between the slippery site and the stimulatory pseudoknot. Changes in the length and composition of this spacer are known to affect rates of À1 PRF (45) , and thus the À1 RF values so determined cannot be taken as absolute. In contrast, the reporters used to monitor mRNA stability contained the native sequences. In light of this, it is likely that the native BUB3 À1 RF signal promotes more frameshifting than the TBF1 signal. Lastly, the SPR6 À1 RF signal is predicted to be quite stable ($À20 kcal/mol), yet promoted very low levels of frameshifting ($0.5%) (15) . Accordingly, destabilization via NMD was negligible for this element, while NGD appeared to be the major contributor.