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 1979, almost simultaneously in human cells and in yeast. This suggested broad phylogenetic conservation and an important biological role. NMD was discovered when it was observed 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 importance of the residues that are not translated. In human genetics, NMD has the potential not only to limit the translation of abnormal proteins but also to occasionally cause detrimental effects in specific genetic mutations.

NMD regulates numerous biological functions in a diverse range of cells, such as contributing to the synaptic plasticity of neurons which shapes adult behavior.