Nonsense‐mediated mRNA Decay


Nonsense‐mediated mRNA decay is the recognition and selective decay of transcripts containing premature termination codons, which occurs in all studied eukaryotic organisms.

Keywords: nonsense‐mediated mRNA decay; nonsense mutation; premature termination codon; mRNA stability; mRNA surveillance

Figure 1.

Premature termination codons (PTCs) are distinguished from genuine termination codons by the presence of downstream cis elements which normally do not occur 3′ of a terminating ribosome. In yeast, the downstream destabilizing element (DSE), which binds Hrp1p, serves this purpose. In mammals, exon–exon junctions, marked by proteins which are deposited concurrent with splicing (postsplicing complexes), provide this function.

Figure 2.

(a) Normal mRNA decay initiates when the poly(A) tail reaches a critical length (∼10 nucleotides) that can no longer support interaction with (PABP). This is thought to destabilize the cap‐binding complex consisting of eukaryotic initiation factor (eIF) 4G, eIF4E and eIF4A. Further rearrangements, requiring the like‐Sm (Lsm) protein complex, ultimately expose the 5′ cap to the decapping enzyme (Dcp1p in yeast). Following removal of the cap, the body of the transcript is rapidly degraded by the exonuclease Xrn1p. (b) Nonsense transcripts are decapped prior to poly(A) tail shortening. The surveillance complex, consisting of Upf1p–3p, is believed directly to destabilize the cap‐binding complex upon encountering a premature termination codon, leading to Dcp1p‐ and Xrn1p‐mediated decay.



Barton‐Davis ER, Cordier L, Shoturma DI, Leland SE and Sweeney HL (1999) Aminoglycoside antibiotics restore dystrophin function to skeletal muscles of mdx mice. Journal of Clinical Investigation 104: 375–381.

Culbertson MR (1999) RNA surveillance: unforeseen consequences for gene expression, inherited genetic disorders, and cancer. Trends in Genetics 15: 74–80.

Frischmeyer PA and Dietz HC (1999) Nonsense‐mediated mRNA decay in health and disease. Human Molecular Genetics 8: 1893–1900.

Gonzalez CI, Ruiz‐Echevarria MJ, Vasudevan S, Henry MF and Peltz SW (2000) The yeast hnRNP‐like protein Hrp1/Nab4 marks a transcript for nonsense‐mediated mRNA decay. Molecular Cell 5: 489–499.

Le Hir H, Izaurralde E, Maquat LE and Moore MJ (2000) The spliceosome deposits multiple proteins 20–24 nucleotides upstream of mRNA exon–exon junctions. The EMBO Journal 19: 6860–6869.

Lelivelt MJ and Culbertson MR (1999) Yeast Upf proteins required for RNA surveillance affect global expression of the yeast transcriptome. Molecular and Cellular Biology 19: 6710–6719.

Li S, Leonard D and Wilkinson MF (1997) T cell receptor (TCR) mini‐gene mRNA expression regulated by nonsense codons: a nuclear‐associated translation‐like mechanism. Journal of Experimental Medicine 185(supplement 6): 985–992.

Lykke‐Andersen J, Shu MD and Steitz JA (2000) Human Upf proteins target an mRNA for nonsense‐mediated decay when bound downstream of a termination codon. Cell 103: 1121–1131.

Maquat LE (1995) When cells stop making sense: effects of nonsense codons of RNA metabolism in vertebrate cells. RNA 1: 453–465.

Medghalchi SM, Frischmeyer PA, Mendell JT, et al. (2001) Rent1, a trans‐effector of nonsense‐mediated mRNA decay, is essential for mammalian embryonic viability. Human Molecular Genetics 10: 99–105.

Mendell JT, Ap Rhys CMJ and Dietz HC (2002) Separable roles for rent1/hUpf1 in altered splicing and decay of nonsense transcripts. Science 298: 419–422.

Mendell JT, Medghalchi SM, Lake RG, Noensie EN and Dietz HC (2000) Novel Upf 2p orthologues suggest a functional link between translation initiation and nonsense surveillance complexes. Molecular and Cellular Biology 20: 8944–8957.

Mitrovich QM and Anderson P (2000) Unproductively spliced ribosomal protein mRNAs are natural targets of mRNA surveillance in C. elegans. Genes & Development 14: 2173–2184.

Wang J, Hamilton JI, Carter MS, Li S and Wilkinson MF (2002) Alternatively spliced TCR mRNA induced by disruption of reading frame. Science 297: 108–110.

Further Reading

Czaplinski K, Ruiz‐Echevarria MJ, Gonzalez CI and Peltz SW (1999) Should we kill the messenger? The role of the surveillance complex in translation termination and mRNA turnover. BioEssays 21: 685–696.

Gallie DR (1998) A tale of two termini: a functional interaction between the termini of an mRNA is a prerequisite for efficient translation initiation. Gene 216: 1–11.

He W and Parker R (2000) Functions of Lsm proteins in mRNA degradation and splicing. Current Opinion in Cell Biology 12: 346–350.

Li S and Wilkinson MF (1998) Nonsense surveillance in lymphocytes? Immunity 8: 135–141.

Priess T and Hentze MW (1999) From factors to mechanisms: translation and translational control in eukaryotes. Current Opinion in Genetics and Development 9: 515–521.

Serin G, Gersappe A, Black JD, Aronoff R and Maquat LE (2001) Identification and characterization of human orthologues to Saccharomyces cerevisiae Upf2 protein and Upf3 protein (Caenorhabitis elegans SMG‐4). Molecular and Cellular Biology 21: 209–223.

Tucker M and Parker R (2000) Mechanisms and control of mRNA decapping in Saccharomyces cerevisiae. Annual Reviews in Biochemistry 69: 571–595.

Web Links

Fibrillin 1 (FBN1); MIM number: 134797. OMIM:‐post/Omim/dispmim?134797

Fibrillin 1 (FBN1); LocusID: 2200. LocusLink:

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Mendell, Joshua T, and Dietz, Harry C(Jan 2006) Nonsense‐mediated mRNA Decay. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0005501]