A patient with a heterozygous nonsense mutation in a tumor suppressor gene has residual mRNA from the mutant allele that contains a premature termination codon (PTC). The cellular quality control mechanism that degrades this abnormal mRNA is:

• A siRNA-mediated RISC cleavage of the mutant mRNA recognizing the PTC sequence
• B No-go decay (NGD) triggered by ribosome stalling at the nonsense codon
• C Non-stop decay (NSD) because the PTC truncates the protein before the poly-A signal
• D Nonsense-mediated mRNA decay (NMD) triggered when ribosomes terminate more than 50–55 nt upstream of an exon junction complex ✓

Explanation

Nonsense-mediated mRNA decay (NMD) is the primary surveillance pathway for PTCs. The rule of 50–55 nt: if a PTC is located more than 50–55 nucleotides upstream of the last exon junction complex (EJC, deposited at splice sites after splicing), the ribosome terminating at the PTC recruits UPF1/UPF2/UPF3 (NMD factors) that interact with the downstream EJC, triggering rapid mRNA degradation. This prevents translation of dominant-negative truncated proteins. No-go decay handles stalled ribosomes from rare codons or secondary structures; non-stop decay handles mRNAs lacking stop codons.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.