Nonsense‐mediated mRNA Decay

Abstract

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 poly(A)‐binding protein (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.

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References

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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.

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Web Links

Fibrillin 1 (FBN1); MIM number: 134797. OMIM: http://www3.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?134797

Fibrillin 1 (FBN1); LocusID: 2200. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=2200

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