nonsense-mediated mRNA decay
Gene expression is highly accurate and rarely generates defective proteins. Several mechanisms ensure this fidelity, including specialized surveillance pathways that rid the cell of mRNAs that are incompletely processed or that lack complete open reading frames.
One such mechanism is nonsense-mediated mRNA decay. It is triggered when ribosomes encounter a premature translation-termination?or nonsense?codon.
Premature termination codons (PTCs) are equivalent to nonsense sequences. They encode no amino acid, and their presence precludes the synthesis of full-length proteins.
The resulting truncated proteins, if synthesized and stable, are likely to be non-functional or might even be deleterious to cellular metabolism.
Approximately one third of genetic and acquired diseases are due to PTCs.
In fact, PTCs are apt to cause at least some cases of all diseases that involve protein insufficiency. Cells have evolved a way to eliminate mRNAs that contain PTCs using a mechanism called nonsense-mediated mRNA decay (NMD).
The specialized factors that are recruited for this process not only promote rapid mRNA degradation, but are also required to resolve a poorly dissociable termination complex.
See also
nonsense-mediated mRNA decay
References
Garneau NL, Wilusz J, Wilusz CJ. The highways and byways of mRNA decay. Nat Rev Mol Cell Biol. 2007 Feb;8(2):113-26. PMID: 17245413
Amrani N, Sachs MS, Jacobson A. Early nonsense: mRNA decay solves a translational problem. Nat Rev Mol Cell Biol. 2006 Jun;7(6):415-25. PMID: 16723977
Kuzmiak HA, Maquat LE. Applying nonsense-mediated mRNA decay research to the clinic: progress and challenges. Trends Mol Med. 2006 Jul;12(7):306-16. PMID: 16782405