Summary
A quality-control pathway that destroys mRNAs with premature stop codons.
In depth
During splicing, exon junction complexes are deposited; if a stop codon lies more than about 50 nt upstream of the last junction, the mRNA is flagged and degraded. It prevents truncated proteins and also regulates normal genes.
NMD is a quality control and a regulatory pathway: about 5 to 10 percent of normal human transcripts are sensitive to it. UPF1, UPF2 and UPF3 proteins detect the stalled ribosome with an exon junction complex downstream, and SMG proteins promote decay.
NMD usually protects: a heterozygous carrier of a nonsense allele makes no truncated protein that could be toxic. But it can also worsen disease where truncated proteins would retain some function, and drugs inhibiting NMD or promoting read-through are being studied. NMD helps explain why some mutations are recessive and others dominant.
Example: in beta-thalassaemia, nonsense mutations early in the gene lead to mRNA degradation and recessive disease, while those in the last exon escape NMD and can be dominant.
Frequently asked questions
What is Nonsense-Mediated Decay?
A quality-control pathway that destroys mRNAs with premature stop codons.
Which area of biology covers Nonsense-Mediated Decay, and how advanced is it?
Nonsense-Mediated Decay is one of the 52 topics in Molecular Biology. It is rated Advanced, so it suits learners who want specialist depth. Related topics in this area include Splicing, Start and Stop Codons, Transcription Factors.
Can you give an example of Nonsense-Mediated Decay?
Many mutations producing premature stop codons cause recessive rather than dominant disease thanks to NMD.
What should I learn before Nonsense-Mediated Decay?
Work through the Beginner topics in Molecular Biology first, such as Central Dogma, DNA Replication, Base Pairing, then return to Nonsense-Mediated Decay. Advanced topics assume the Intermediate vocabulary.
What topics are related to Nonsense-Mediated Decay?
The closest topics to Nonsense-Mediated Decay are Splicing, Start and Stop Codons, Transcription Factors, microRNA. Comparing them side by side is a good way to see how the ideas connect.
How can I check that I understand Nonsense-Mediated Decay?
Read the summary and the in-depth section, then use the quick check on the interactive lesson for Nonsense-Mediated Decay. To practise the whole of Molecular Biology, use the Molecular Biology quiz.
How is Nonsense-Mediated Decay different from Splicing?
Nonsense-Mediated Decay: A quality-control pathway that destroys mRNAs with premature stop codons. Splicing: The removal of introns and joining of exons by the spliceosome to produce mature mRNA. Read both side by side and note what each one explains.
How should I study Nonsense-Mediated Decay step by step?
First, read the summary and write the definition in your own words. Second, read the in-depth section and note any example. Third, compare it with Splicing and explain the difference aloud. Finally, take the Molecular Biology quiz and come back to this page for any question you miss.