Nonsense-mediated decay

Canonical NMD pathway (in humans)

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.[1] Translation of these aberrant mRNAs could, in some cases, lead to deleterious gain-of-function or dominant-negative activity of the resulting proteins.[2]

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.[3] NMD was discovered when it was realized that cells often contain unexpectedly low concentrations of mRNAs that are transcribed from alleles carrying nonsense mutations.[4] 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.[5]

NMD functions to regulate numerous biological functions in a diverse range of cells, including the synaptic plasticity of neurons which may shape adult behavior.[6]

  1. ^ Baker KE, Parker R (June 2004). "Nonsense-mediated mRNA decay: terminating erroneous gene expression". Current Opinion in Cell Biology. 16 (3): 293–299. doi:10.1016/j.ceb.2004.03.003. PMID 15145354.
  2. ^ Chang YF, Imam JS, Wilkinson MF (2007). "The nonsense-mediated decay RNA surveillance pathway". Annual Review of Biochemistry. 76: 51–74. doi:10.1146/annurev.biochem.76.050106.093909. PMID 17352659. S2CID 2624255.
  3. ^ Kulozik A. "Research Focus 1: Nonsense Mediated Decay (NMD)". Molecular Medicine Partnership Unit. University of Heidelberg. Archived from the original on 2016-11-17. Retrieved 2014-11-17.
  4. ^ Sharma J, Keeling KM, Rowe SM (August 2020). "Pharmacological approaches for targeting cystic fibrosis nonsense mutations". European Journal of Medicinal Chemistry. 200: 112436. doi:10.1016/j.ejmech.2020.112436. PMC 7384597. PMID 32512483.
  5. ^ Holbrook JA, Neu-Yilik G, Hentze MW, Kulozik AE (August 2004). "Nonsense-mediated decay approaches the clinic". Nature Genetics. 36 (8): 801–808. doi:10.1038/ng1403. PMID 15284851. S2CID 23188275.
  6. ^ Notaras M, Allen M, Longo F, Volk N, Toth M, Li Jeon N, et al. (December 2020). "UPF2 leads to degradation of dendritically targeted mRNAs to regulate synaptic plasticity and cognitive function". Molecular Psychiatry. 25 (12): 3360–3379. doi:10.1038/s41380-019-0547-5. PMC 7566522. PMID 31636381. S2CID 204812259.