Nonsense-mediated decay

Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that exists in all eukaryotes. Its main function is to reduce errors in gene expression by eliminating mRNA transcripts that contain premature stop codons. Translation of these aberrant mRNAs could, in some cases, lead to deleterious gain-of-function or dominant-negative activity of the resulting proteins.

NMD was first described in human cells and in yeast almost simultaneously in 1979. This suggested broad phylogenetic conservation and an important biological role of this intriguing mechanism. NMD was discovered when it was realized that cells often contain unexpectedly low concentrations of mRNAs that are transcribed from alleles carrying nonsense mutations. Nonsense mutations code for a premature stop codon which causes the protein to be shortened. The truncated protein may or may not be functional, depending on the severity of what is not translated. In human genetics, NMD has the possibility to not only limit the translation of abnormal proteins, but it can occasionally cause detrimental effects in specific genetic mutations.

NMD functions to regulate numerous biological functions in a diverse range of cells, including the synaptic plasticity of neurons which may shape adult behavior.