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Biochim Biophys Acta. 2013 Jun-Jul;1829(6-7):624-33. doi: 10.1016/j.bbagrm.2013.03.002. Epub 2013 Mar 13.

Regulation of nonsense-mediated mRNA decay: implications for physiology and disease.

Author information

1
Department of Reproductive Medicine, University of California, San Diego, CA 92093-0864, USA.

Abstract

Nonsense-mediated mRNA decay (NMD) is an mRNA quality control mechanism that destabilizes aberrant mRNAs harboring premature termination (nonsense) codons (PTCs). Recent studies have shown that NMD also targets mRNAs transcribed from a large subset of wild-type genes. This raises the possibility that NMD itself is under regulatory control. Indeed, several recent studies have shown that NMD activity is modulated in specific cell types and that key components of the NMD pathway are regulated by several pathways, including microRNA circuits and NMD itself. Cellular stress also modulates the magnitude of NMD by mechanisms that are beginning to be understood. Here, we review the evidence that NMD is regulated and discuss the physiological role for this regulation. We propose that the efficiency of NMD is altered in some cellular contexts to regulate normal biological events. In disease states-such as in cancer-NMD is disturbed by intrinsic and extrinsic factors, resulting in altered levels of crucial NMD-targeted mRNAs that lead to downstream pathological consequences. This article is part of a Special Issue entitled: RNA Decay mechanisms.

PMID:
23500037
PMCID:
PMC3660545
DOI:
10.1016/j.bbagrm.2013.03.002
[Indexed for MEDLINE]
Free PMC Article

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