title: Nonsense-mediated mRNA decay in humans at a glance.
abstract: Nonsense-mediated mRNA decay (NMD) is an mRNA quality-control mechanism that typifies all eukaryotes examined to date. NMD surveys newly synthesized mRNAs and degrades those that harbor a premature termination codon (PTC), thereby preventing the production of truncated proteins that could result in disease in humans. This is evident from dominantly inherited diseases that are due to PTC-containing mRNAs that escape NMD. Although many cellular NMD targets derive from mistakes made during, for example, pre-mRNA splicing and, possibly, transcription initiation, NMD also targets ∼10% of normal physiological mRNAs so as to promote an appropriate cellular response to changing environmental milieus, including those that induce apoptosis, maturation or differentiation. Over the past ∼35 years, a central goal in the NMD field has been to understand how cells discriminate mRNAs that are targeted by NMD from those that are not. In this Cell Science at a Glance and the accompanying poster, we review progress made towards this goal, focusing on human studies and the role of the key NMD factor up-frameshift protein 1 (UPF1).
authors.affiliation: Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA Center for RNA Biology, University of Rochester, Rochester, NY 14642, USA.
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Kurosaki
authors.affiliation: Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA Center for RNA Biology, University of Rochester, Rochester, NY 14642, USA lynne_maquat@urmc.rochester.edu.
authors.forename: Lynne E
authors.initials: LE
authors.lastname: Maquat
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D018389:Codon, Nonsense / Q000235:genetics; D006801:Humans; D059365:Nonsense Mediated mRNA Decay / Q000235:genetics*; D020365:RNA Helicases; D012333:RNA, Messenger / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics
chemical_list: D018389:Codon, Nonsense; D012333:RNA, Messenger; D015534:Trans-Activators; D020365:RNA Helicases; C101828:UPF1 protein, human
keywords: NMD; RNA quality control; Superfamily 1 ATP-dependent RNA helicase; UPF1 protein; mRNA surveillance