medium · MCAT Biological & Biochemical Foundations of Living Systems
A nonsense mutation introduces a premature stop codon in the middle of the second exon of a multi-exon gene. Surprisingly, a patient heterozygous for this allele shows almost no protein from that allele rather than a truncated protein.
The most likely explanation is that the transcript is degraded by:
- Nonsense-mediated decay, triggered because a stop codon lies upstream of an exon-junction complex remaining after the first round of translation
- RNA interference, because the premature stop creates a double-stranded region recognized by Dicer and the RISC complex
- Deadenylation-independent 5' decapping triggered directly by the ribosome stalling at the premature stop codon
- No-go decay, because the ribosome stalls on a stable secondary structure created by the point mutation
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