Fig. 1

Simplified representation of the nonsense-mediated mRNA decay (NMD) model in mammalian cells. a When the ribosome stops at a premature termination codon (PTC), the interaction of UPF1 and eRF3 induces premature translation termination. b After this interaction, the SURF complex is formed by eRF1, eRF3, SMG1 associated with SMG8 and SMG9, DHX34 and UPF1. c Then, UPF1 interacts with UPF2-UPF3B, either bound to the EJC downstream of the PTC (EJC-dependent NMD model) or diffused in the cytoplasm (EJC-independent NMD model), to form the DECID complex and induces the SMG1-mediated phosphorylation of UPF1. At this point, translation has terminated with the dissociation of the ribosomal subunits, the release factors and the nascent peptide. d Phosphorylated UPF1 triggers the decay phase by recruiting factors that lead to mRNA degradation, such as SMG6, which produces an endonucleolytic cleavage, SMG5-SMG7 dimer, which recruits the CCR4-NOT deadenylase complex, and/or PNRC2, which recruits the decapping complex (DCPC)