Nonsense-mediated decay


Nonsense-mediated decay

Nonsense-mediated decay (NMD) is a cellular mechanism of mRNA surveillance that functions to detect nonsense mutations and prevent the expression of truncated or erroneous proteins. Following transcription, precursor mRNA undergoes an assemblage of ribonucleoprotein (RNP) components followed by regulatory pre-mRNA processing. Large average intron size in eukaryotic cells greatly increases the probability that aberrant mRNA splicing will result in the presence of a nonsense (stop) codon (UAA, UAG, UGA) somewhere within the open reading frame. NMD is triggered by exon junction complexes (EJCs) (components of the assembled RNP) that are deposited during pre-mRNA processing. While EJCs located in an open reading frame upstream of exon-exon junctions may facilitate ribosomal recruitment[1] prior to displacement by a "pioneer" round of translation[2], EJCs located downstream of a nonsense codon are not displaced because the ribosome is released from the transcript before reaching it. These remaining EJCs function as tags for recruitment of UPF1 following the mRNA's transport out of the nucleus and into the cytosol where the RNA is degraded, for example by the exosome complex[3]. NMD is not only a mechanism for degrading aberrant mRNA, however, as there are numerous examples of normal transcripts whose expression is regulated by this process[4] including the plasticity protein Arc/Arg3.1.

See also

References

  1. ^ Nott A, Le Hir H, Moore MJ (2004). "Splicing enhances translation in mammalian cells: an additional function of the exon junction complex.". Genes Dev 18 (2): 210–222. doi:10.1101/gad.1163204. PMC 324426. PMID 14752011. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=324426. 
  2. ^ Ishigaki Y, Li, X, Serin G, Maquat LE (2001). "Evidence for a pioneer round of mRNA translation: mRNAs subject to nonsense-mediated decay in mammalian cells are bound by CBP80 and CBP20.". Cell 106 (5): 607–617. doi:10.1016/S0092-8674(01)00475-5. PMID 11551508. 
  3. ^ Chang et al.; Imam, JS; Wilkinson, MF (2007). "The nonsense-mediated decay RNA surveillance pathway". Annu Rev Biochem. 76: 51–74. doi:10.1146/annurev.biochem.76.050106.093909. PMID 17352659. 
  4. ^ Mendell JT, Sharifi NA, Meyers JL, Martinez-Murillo F, Dietz HC (2004). "Nonsense surveillance regulates expression of diverse classes of mammalian transcripts and mutes genomic noise.". Nature Genetics 36 (10): 1073–1078. doi:10.1038/ng1429. PMID 15448691. 

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