Figure 2.

Exon junction complex (EJC)-dependent and -independent nonsense-mediated mRNA decay (NMD) mechanisms. In the classical model, UPF1, SMG1 complex, eRF1, and eRF3 form the SURF complex. Subsequently, the SURF complex binds to UPF2, UPF3b, and the EJC proteins to form the decay-inducing (DECID) complex. UPF1 is phosphorylated and activated by SMG1. In the EJC-independent model, NMD activation is triggered by the presence of a long 3′UTR. In both cases, phosphorylated UPF1 recruits either SMG6 or the SMG5:SMG7 complex to initiate endonucleolytic or exonucleolytic mRNA decay, respectively. In the figure, the illustration of SMG6 and SMG5:SMG7 recruitment and transcript degradations follow classical NMD. In EJC-independent NMD, UPF2 and UPF3b should not exist. The dashed boxes indicate that there are UPF2- and UPF3b-independent NMD pathways.