In contrast, the steady-state abundance of the EST2 and BUB3 À1 RF signal-containing reporter mRNAs were increased in both the upf1D and dom34D mutants: the EST2 signal was 35-fold less effective in decreasing mRNA abundance in upf1D cells when compared to the WT strain and $14-fold less effective in dom34D cells, while the values for the BUB3 signal were $7-fold and 8-fold, respectively. The steady-state abundance of the SPR6 À1 RF signal containing reporter mRNA was primarily increased in dom34D cells ($2.0-fold). Deletion of DCP1, XRN1 and SKI3, all of which function downstream of UPF1 or DOM34, also generally increased the abundance of the reporter mRNAs ( Figure 2D -F). We note however that, in the case of the dcp1D cells, the reporter mRNAs were relatively abundant, most likely because of the presence of the 3 0 ! 5 0 exonuclease activity of the exosome, and/or due to decapping activity contributed by other factors, e.g. by the presence of the L-A virus (29) . These results establish that endogenous cellular À1 RF signals can decrease mRNA steady-state abundance in yeast through the NMD pathway. In addition, the data are consistent with the hypothesis that a subset of these signals may also affect mRNA abundance through NGD, although substantiation of this claim requires further studies, e.g. to monitor the abundance of the endonucleolytic cleavage products and mRNA stability assays in NGD À strains.