The complexity of the nonsense-mediated decay (NMD)
system makes it difficult to study by comparing the expression
of various single reporter constructs. The known effects
of the NMD genes include a reduction both in mRNA
stability (reviewed by Czaplinski et al., 1999) and in
the efficiency of translational initiation (Muhlrad &
Parker, 1999) of nonsense-containing plasmids as well as
an apparent increase in the efficiency of translational
termination as evidenced by increased readthrough of nonsense
mutations (Bidou et al., 2000; Maderazo et al., 2000).
The single reporter system can not distinguish among these
effects and inference is required to determine which mechanism
underlies any observed phenotypic effect on gene expression.
It is particularly problematic to differentiate the effects
of translation initiation accuracy from putative effects
on translational frameshifting. The dual reporter system
used in our work isolates the effect of translational frameshifting
from effects on mRNA stability, initiation or termination.
Much is made by Dinman et al. of the relative effects of
various mutations, yet it remains unclear whether these
are fundamental differences or simply differences in phenotypic
strength of the various mutations.