medium · MCAT bio-biochem

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:

  1. Nonsense-mediated decay, triggered because a stop codon lies upstream of an exon-junction complex remaining after the first round of translation
  2. RNA interference, because the premature stop creates a double-stranded region recognized by Dicer and the RISC complex
  3. Deadenylation-independent 5' decapping triggered directly by the ribosome stalling at the premature stop codon
  4. No-go decay, because the ribosome stalls on a stable secondary structure created by the point mutation

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