Nonsense-mediated decay is an mRNA surveillance pathway that eliminates mRNAs with premature stop codons. How does the cell distinguish between normal mRNAs and those with a premature stop?

Question: Explain how the nonsense-mediated mRNA decay (NMD) pathway distinguishes between normal mRNAs and those with a premature stop codon, and how it eliminates faulty mRNAs. Answer: The NMD pathway distinguishes between normal mRNAs and those with a premature stop codon by checking for the presence of an Exon Junction Complex (EJC) near the stop codon. In normal mRNAs, the stop codon is located after the last exon junction, and all EJCs are displaced by ribosomes during translation. In contrast, premature stop codons are located before the last EJC, which leads to close proximity between the ribosome, EJC, and stop codon. This proximity recruits additional factors, such as Upf1, Upf2, and Upf3, to form the NMD complex, which interacts with release factors and triggers rapid degradation of the faulty mRNA.