Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/82008
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Type: Journal article
Title: Nonsense-mediated mRNA decay: Inter-individual variability and human disease
Author: Nguyen, L.
Wilkinson, M.
Gecz, J.
Citation: Neuroscience and Biobehavioral Reviews, 2014; 46(Part 2):175-186
Publisher: Pergamon-Elsevier Science Ltd
Issue Date: 2014
ISSN: 0149-7634
1873-7528
Statement of
Responsibility: 
Lam Son Nguyen, Miles F. Wilkinson, Jozef Gecz
Abstract: Nonsense-mediated mRNA decay (NMD) is a regulatory pathway that functions to degrade transcripts containing premature termination codons (PTCs) and to maintain normal transcriptome homeostasis. Nonsense and frameshift mutations that generate PTCs cause approximately one-third of all known human genetic diseases and thus NMD has a potentially important role in human disease. In genetic disorders in which the affected genes carry PTC-generating mutations, NMD acts as a double-edge sword. While it can benefit the patient by degrading PTC-containing mRNAs that encode detrimental, dominant-negative truncated proteins, it can also make the disease worse when a PTC-containing mRNA is degraded that encodes a mutant but still functional protein. There is evidence that the magnitude of NMD varies between individuals, which, in turn, has been shown to correlate with both clinical presentations and the patients' responses to drugs that promote read-through of PTCs. In this review, we examine the evidence supporting the existence of inter-individual variability in NMD efficiency and discuss the genetic factors that underlie this variability. We propose that inter-individual variability in NMD efficiency is a common phenomenon in human populations and that an individual's NMD efficiency should be taken into consideration when testing, developing, and making therapeutic decisions for diseases caused by genes harboring PTCs.
Keywords: Nonsense-mediated mRNA decay; Inter-individual NMD efficiency; Regulation of NMD; Expression quantitative trait loci; Copy number variation; Staufen-mediated mRNA decay; miR-128; miR-125
Rights: © 2013 Elsevier Ltd. All rights reserved.
RMID: 0020138425
DOI: 10.1016/j.neubiorev.2013.10.016
Appears in Collections:Paediatrics publications

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