Degradation pathways activated in NMD. Once the PTC has been recognized, phosphorylated UPF1 will be able to interact with different partners such as the heterodimers SMG5/SMG7 and SMG5/PNRC2. The latter is then capable of activating the decapping complex (DC) in order to remove the 5’ cap bound by the cap binding protein (CBP) that can be CBP80/CBP20 or eIF4E. The heterodimers SMG5/SMG7 can also trigger 3’ deadenylation via the CCR4-NOT complex. Phosphorylated UPF1 can also interact with the SMG6 protein which, through its endonucleolytic activity, induces a cut in the vicinity of the PTC, releasing unprotected 5’ and 3’ ends (upper panel). Exoribonucleases then come into play and degrade the mRNA from the 5’ and 3’ ends generated in the previous step. These degradations involve the XRN1 protein, which has 5’-to-3’ activity, and the exosome, which degrades the RNA in the 3’-to-5’ direction (lower panel).
