Fig. 2.

Model for degradation of PTC carrying transcripts. Step 1 Translation is initiated at the AUG start codon. The ribosome starts translation in the 5′ to 3′ direction. Step 2 When the translating ribosome stalls at a PTC, eRF1 and eRF3 interact with and bind to the ribosome. The physical distance between poly(A)-bound PABPC1 and the stalled ribosome is too large for efficient interaction and subsequent translation termination. Step 3 Since the interaction between PABPC1 and eRF3 is inefficient in this scenario, UPF1 is able to interact with eRF3 instead. Furthermore, the EJC serves as a binding platform for UPF3b and UPF2. Additionally, SMG1 is recruited to UPF1. SMG1 not only interacts with UPF1 and UPF2 but also phosphorylates UPF1. Step 4 Phosphorylated UPF1 recruits the SMG5/7 heterodimer as well as the endonuclease SMG6. The stalling ribosome has been removed from the transcript by this point. SMG6 cleaves the transcript in close proximity of the PTC, whereas SMG5/7 recruit the catalytic subunit of the CCR4-NOT deadenylase complex POP2. Step 5 The NMD factors are removed from the cleaved transcript and decapping and deadenylation commences. As a last step, the exonuclease XRN1 is recruited and degrades the transcript in 5′ to 3′ direction, and the exosome supposedly mediates 3′ to 5′ degradation