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?

Verified step by step guidance

Understand that nonsense-mediated decay (NMD) targets mRNAs containing premature stop codons (also called nonsense codons) to prevent the production of truncated, potentially harmful proteins.

Recognize that during normal mRNA processing, exon junction complexes (EJCs) are deposited upstream of exon-exon junctions after splicing.

Know that during the first round of translation, the ribosome removes EJCs as it moves along the mRNA.

Identify that if a stop codon is encountered before the last EJC is removed (i.e., upstream of an EJC), the cell recognizes this as a premature stop codon, triggering NMD.

Conclude that the presence of an EJC downstream of a stop codon acts as a signal for the cell to distinguish premature stop codons from normal stop codons, leading to degradation of the faulty mRNA.

Key Concepts

Here are the essential concepts you must grasp in order to answer the question correctly.

Nonsense-Mediated Decay (NMD) Pathway

NMD is a cellular quality control mechanism that detects and degrades mRNAs containing premature stop codons to prevent the production of truncated, potentially harmful proteins. It ensures only properly processed mRNAs are translated, maintaining protein integrity.

Premature Stop Codons and Their Recognition

Premature stop codons occur when a stop signal appears earlier than expected in the mRNA sequence, often due to mutations. The cell distinguishes these by their position relative to downstream exon-exon junctions marked by exon junction complexes (EJCs), which are key signals in identifying faulty mRNAs.

Exon Junction Complexes (EJCs) and mRNA Surveillance

EJCs are protein complexes deposited near exon-exon junctions after splicing. During the pioneer round of translation, if a stop codon is detected upstream of an EJC, the mRNA is flagged as abnormal, triggering NMD. This spatial relationship helps the cell differentiate normal from premature stop codons.