Nonsense-mediated decay

Definition

Nonsense-mediated decay (NMD) is a cellular mechanism that identifies and degrades mRNA transcripts containing premature stop codons, preventing the production of potentially harmful truncated proteins. This quality control process is essential for maintaining the integrity of gene expression by ensuring that only properly processed mRNA is translated into proteins. By eliminating faulty mRNA, NMD plays a crucial role in regulating post-transcriptional gene expression in eukaryotic cells.

5 Must Know Facts For Your Next Test

1. Nonsense-mediated decay targets mRNAs with premature stop codons that can arise from mutations or errors in transcription.
2. The process of NMD helps prevent the accumulation of defective proteins, which could disrupt cellular functions or lead to diseases.
3. NMD is initiated when ribosomes encounter a stop codon upstream of the exon junction complex during translation, signaling the need for degradation.
4. This mechanism is highly conserved across eukaryotic organisms, highlighting its importance in gene regulation and cellular health.
5. In addition to preventing the expression of faulty proteins, NMD can also regulate the levels of certain normal mRNAs by controlling their stability.

Review Questions

• How does nonsense-mediated decay function at the molecular level, and what triggers this process?
  • Nonsense-mediated decay functions by detecting mRNA transcripts that contain premature stop codons. When ribosomes translate an mRNA molecule and encounter a stop codon located upstream of an exon junction complex, this signals that the transcript may be faulty. The presence of this incorrect stop codon triggers a series of molecular interactions that lead to the recruitment of decay factors, ultimately resulting in the degradation of the faulty mRNA.
• Discuss the implications of nonsense-mediated decay on protein synthesis and cellular function.
  • Nonsense-mediated decay has significant implications for protein synthesis and cellular function by ensuring that only properly processed mRNAs are translated into proteins. By degrading mRNAs with premature stop codons, NMD prevents the production of truncated proteins that could be nonfunctional or harmful to the cell. This quality control mechanism is vital for maintaining cellular health, as defective proteins can disrupt normal biological processes and contribute to various diseases.
• Evaluate the role of nonsense-mediated decay in the context of genetic diseases caused by mutations that introduce premature stop codons.
  • Nonsense-mediated decay plays a critical role in the context of genetic diseases by targeting and degrading mRNAs with mutations that introduce premature stop codons. In conditions such as cystic fibrosis or Duchenne muscular dystrophy, where specific mutations can lead to truncated proteins, NMD acts as a defense mechanism against potentially harmful effects. However, this process can also exacerbate disease symptoms if important mRNAs are degraded along with those containing harmful mutations, emphasizing the need for balanced regulation in cellular environments.

Related terms

Premature Stop Codon: A mutation in an mRNA sequence that creates a stop codon earlier than expected, leading to incomplete protein synthesis.

mRNA Surveillance: A set of mechanisms that monitor the quality of mRNA molecules and ensure that only correctly processed mRNA is used for protein synthesis.

Exon Junction Complex: A protein complex that assembles at the junctions of exons during splicing, playing a key role in the recognition of properly processed mRNA and in the activation of NMD.