Figure 1. Recognition of NMD surveillance targets.

(a) Canonical termination. Capped and polyadenylated messages are translated through the open reading frame until recognition of a stop codon by the eukaryotic release factors, eRF1 and eRF3. Close proximity of authentic stop codons with the poly(A) tail is proposed to facilitate interactions between eRF3 and poly(A)-binding proteins (PABP) that positively contribute to peptide release. (b) Nonsense-mediated decay (NMD). In the case of a premature stop codon (PTC), lack of proximity is proposed to disrupt interaction between eRF3 and PABP. Canonical termination is further modified by the presence of NMD factors. In the EJC model of higher eukaryotes, this results from encountering a stop codon upstream of an exon-junction complex (EJC). In this model, communication between the termination factors and the EJC is effectively bridged by Upf1 in coordination with Upf2 and Upf3. In the 3′ UTR model, a PTC effectively extends the de facto 3′ untranslated region (UTR) of the message. This provides a larger binding platform for Upf1, which drives the termination event towards NMD rather than classical termination. Thick line, open reading frame; thin line, 5′ and 3′ UTR.