title: The nonsense-mediated decay RNA surveillance pathway.
abstract: Nonsense-mediated mRNA decay (NMD) is a quality-control mechanism that selectively degrades mRNAs harboring premature termination (nonsense) codons. If translated, these mRNAs can produce truncated proteins with dominant-negative or deleterious gain-of-function activities. In this review, we describe the molecular mechanism of NMD. We first cover conserved factors known to be involved in NMD in all eukaryotes. We then describe a unique protein complex that is deposited on mammalian mRNAs during splicing, which defines a stop codon as premature. Interaction between this exon-junction complex (EJC) and NMD factors assembled at the upstream stop codon triggers a series of steps that ultimately lead to mRNA decay. We discuss whether these proofreading events preferentially occur during a "pioneer" round of translation in higher and lower eukaryotes, their cellular location, and whether they can use alternative EJC factors or act independent of the EJC.
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. yjchang@mdanderson.org
authors.forename: Yao-Fu
authors.initials: YF
authors.lastname: Chang
authors.forename: J Saadi
authors.initials: JS
authors.lastname: Imam
authors.forename: Miles F
authors.initials: MF
authors.lastname: Wilkinson
mesh_terms: D000818:Animals; D003062:Codon; D005091:Exons; D006801:Humans; D046912:Multiprotein Complexes; D020125:Mutation, Missense; D014176:Protein Biosynthesis; D020365:RNA Helicases; D012326:RNA Splicing; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D003062:Codon; D046912:Multiprotein Complexes; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C468286:UPF2 protein, human; C435487:UPF3A protein, human; D020365:RNA Helicases; C101828:UPF1 protein, human