Nonsense mediated decay (NMD) is a cellular mechanism of mRNA surveillance to detect nonsense mutations and prevent the expression of truncated or erroneous proteins. In mammals, NMD is triggered by exon-junction complexes (EJC), which are initially deposited during pre-mRNA splicing. Normally, an EJC is removed by the ribosome during the first round of translation of the mRNA. However, if an EJC occurs downstream of the nonsense codon, then the EJC is still bound to the mRNA when the ribosome reaches the nonsense codon, and thus can serve to trigger NMD. The presence of a downstream EJC is identified as a problem by NMD factors and the RNA is degraded, for example by the exosome complex. 1 With few exceptions, an EJC is not deposited downstream of normal stop codon.
In other organisms, including yeast and drosophila melanogaster, NMD is triggered by a completely different mechanism. The key to this mechanism appears to be the sequence of the mRNA downstream of either premature stop codons or natural stop codons.
The Vega project uses the following metric to classify a transcript in their database as a candidate for NMD: "If the coding sequence ... of a transcript finishes >50bp from a downstream splice site then it is tagged as NMD."2
