In Saccharomyces cerevisiae, nonsense-mediated mRNA decay (NMD) requires Upf1p, 
Upf2p, and Upf3p to accelerate the decay rate of two unique classes of 
transcripts: (1) nonsense mRNAs that arise through errors in gene expression, 
and (2) naturally occurring transcripts that lack coding errors but have 
built-in features that target them for accelerated decay (error-free mRNAs). NMD 
can trigger decay during any round of translation and can target Cbc-bound or 
eIF-4E-bound transcripts. Extremely low concentrations of the Upf proteins 
relative to the total pool of transcripts make it difficult to understand how 
nonsense transcripts are selectively recruited. To stimulate debate, we propose 
two alternative mechanisms for selecting nonsense transcripts for NMD and for 
assembling components of the surveillance complex, one for the first (pioneer) 
round of translation, called "nuclear marking," and the other for subsequent 
rounds, called "reverse assembly." The model is designed to accommodate (1) the 
low abundance of NMD factors, (2) the role of nucleocytoplasmic shuttling 
proteins in NMD, (3) the independent and nonobligate order of assembly of two 
different subcomplexes of NMD factors, and (4) the ability of NMD to 
simultaneously reduce or eliminate the synthesis of truncated proteins produced 
by nonsense transcripts while down-regulating but not completely eliminating 
functional proteins produced from error-free NMD-sensitive transcripts