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Fig. 1. Nonsense-mediated decay. (A) The phenomenon. The gene (with promoter, parts of the first and penultimate exons, and last exon), primary transcript, spliced mRNA (with an exon junction complex – EJC – deposited 5' of the exon-exon junction) and protein are shown. UPF proteins associate with the EJC (not shown). (i) Transcription of a gene with a termination codon in the correct place leads to a spliced and stable mRNA, and a full-length protein. (ii) Moving the termination codon 5' to what will become an exonexon junction leads to an unstable mRNA and a truncated protein. (B) Models for NMD. In each case, an mRNA encoding a PTC is made at the transcription site by a polymerase (pol). The mRNA with its EJC then passes through the nucleoplasm to dock at the membrane, before exiting through the pore to the cytoplasm. The mRNA is destroyed once the NMD machinery detects the PTC. (i) A cytoplasmic ribosome detects the PTC, and transmits a signal to the nucleus that leads to degradation of homologous transcripts containing the PTC. (ii) NMD occurs as the transcript bearing the PTC emerges into the cytoplasm. (iii) Some unknown nuclear mechanism (black box) recognizes the PTC and destroys the mRNA. (iv) A ribosome detects the PTC in the nascent transcript at the transcription site.
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