title: Nonsense-mediated mRNA decay modulates clinical outcome of genetic disease.
abstract: The nonsense-mediated decay (NMD) pathway is an mRNA surveillance system that typically degrades transcripts containing premature termination codons (PTCs) in order to prevent translation of unnecessary or aberrant transcripts. Failure to eliminate these mRNAs with PTCs may result in the synthesis of abnormal proteins that can be toxic to cells through dominant-negative or gain-of-function effects. Recent studies have expanded our understanding of the mechanism by which nonsense transcripts are recognized and targeted for decay. Here, we review the physiological role of this surveillance pathway, its implications for human diseases, and why knowledge of NMD is important to an understanding of genotype-phenotype correlations in various genetic disorders.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Khajavi
authors.forename: Ken
authors.initials: K
authors.lastname: Inoue
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
mesh_terms: D000483:Alleles; D000818:Animals; D018389:Codon, Nonsense / Q000235:genetics*; D018388:Codon, Terminator; D005799:Genes, Dominant; D005808:Genes, Recessive; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D006801:Humans; D010641:Phenotype; D020365:RNA Helicases; D012333:RNA, Messenger / Q000235:genetics*; D015534:Trans-Activators / Q000502:physiology
chemical_list: D018389:Codon, Nonsense; D018388:Codon, Terminator; C460979:NMD-F protein, human; D012333:RNA, Messenger; D015534:Trans-Activators; D020365:RNA Helicases; C101828:UPF1 protein, human