Figure 3.

During NMD, interaction of CBP80 with the UPF1 promotes the joining of SMG1-UPF1 to eRF1-eRF3 at a PTC to form SURF and, subsequently, the joining of SMG1-UPF1 to a PTC-distal EJC. At the point when ribosomes engaged in the pioneer round of translation reach a PTC, CBP80 of CBC interacts directly but transiently or weakly with the NMD factor UPF1 (Hwang et al. 2010). It is unclear whether UPF1 is already associated with its kinase SMG1. Interaction of CBP80-UPF1 augments the binding of UPF1 and SMG1 to the heterodimer of eRF1 and eRF3 that is poised at the PTC. Binding forms the SURF complex. It is possible, but not certain, that the same UPF1 molecule that associates with CBP80 also ends up in SURF. Joining of SMG1-UPF1 to eRF1–eRF3 appears to be in competition with joining of poly(A)-tail-bound PABPC1 to eRF1-eRF3, the latter of which likely occurs predominantly at termination codons that do not trigger NMD (Ivanov et al. 2008; Singh et al. 2008). CBP80 subsequently promotes the joining of SMG1-UPF1 to a PTC-distal EJC, which generally consists of NMD factors UPF2 and either UPF3 or UPF3X. Contrary to some (Ya-mashita et al. 2009) but consistent with other (Kashima et al. 2006) published data, we found no convincing evidence that eRF1 or eRF3 also join the EJC, although we are able to detect an association of CBP80 with the EJC (Hwang et al. 2010). SMG1-UPF1 binding to the EJC triggers UPF1 phosphorylation (circled “P”), which inhibits further translation initiation events at the mRNA 5′ end and enhances the efficiency of mRNA decay (Kashima et al. 2006; Isken et al. 2008). (AUG) translation initiation codon. (Normal ter) normal termination codon; not shown is PABPN1 at the poly(A) tail, which is present concomitantly with PABPC1.