Figure 1. NMD pathway.
(A) Simplified model for translation in the proper mRNP (messenger ribonucleoprotein) environment. In the case of mRNAs with a normal stop codon, signals from the 3′-UTR (untranslated region) and the poly(A) tail (RNA features and/or RNA-binding proteins) allow the proper termination of translation and reinitiation of the ribosome at the start codon. (B) Simplified model for assembly of the NMD machinery on an NMD target. When a stop codon fails to get the signals from the 3′-UTR and the poly(A) tail (PTC), the ribosome stalls and the NMD factor Upf1 is recruited by the termination factors. The kinase Smg1 is also incorporated and phosphorylates Upf1, committing the PTC-containing mRNA to NMD. Upf2 and, to a lesser extent, Upf3 are necessary for Upf1 phosphorylation. In some cases, events such as the presence of the EJC downstream of the PTC enhance the recognition of the mRNA as an NMD target (e.g. by facilitating Upf2 and Upf3 recruitment). Phosphorylated Upf1 interacts with the other Smg factors, Smg5, Smg6 and Smg7, and mRNA degradation is initiated. eRF, eukaryotic translation release factor; PABP, poly(A)-binding protein.