The dynamic interactions between virus infections and nonsense-mediated decay

Figures

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  Figure 1. Recognition of transcript features by nonsense-mediated decay. During splicing in the nucleus, exon junction complexes (EJCs) consisting of eukaryotic translation initiation factor 4A3 (eIF4A3), MAGOH, Y14 (also called RBM8A), and the NMD factors UPF2 and UPF3b are deposited onto the RNA transcript at exon-exon junctions. (A) Normal translation. Following translocation into the cytosol through the nuclear pore complex (NPC), the translating ribosome removes the EJC, preventing NMD induction and leading to the recycling of the EJC components back into the nucleus by the actions of PYM1. (B) EJC-dependent NMD. Upon encountering a premature termination codon (PTC) more than 50–55 nucleotides upstream of the EJC, the stalled ribosome is physically incapable of removing the EJC. The presence of the EJC and the long distance to polyadenylate-binding protein 1 (PABPC) hinder efficient translation termination at the PTC, leading to recruitment and activation of the core NMD factor UPF1 and the induction of transcript degradation. (C) EJC-independent NMD. The presence of a long 3′-UTR interferes with the interactions between the terminating ribosome and PABPC. This increases the chance…

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  Figure 2. The nonsense-mediated decay RNA degradation process. (1) Following binding of activated UPF1, the SMG1-8-9 complex is recruited to RNA transcripts. (2) SMG1 is subsequently released from SMG8-9, activating SMG1’s kinase activity and enabling phosphorylation of UPF1 at residues T28 and S1096, providing docking sites for SMG6 (T28) and the SMG5:SMG7 heterodimer (S1096). (3) The SMG5:SMG7 heterodimer complex recruits decapping protein 1 (Dcp1), the 5′-3′ exonuclease Xrn1, the CCR4-NOT complex, and protein phosphatase 2 (PP2A). Together, these factors induce the dephosphorylation of UPF1 and initiate mRNA degradation in P-bodies. (4) Finally, the NMD complex disassociates from the degraded RNA transcript and the individual components are recycled for another round of NMD.