title: Nonsense-Mediated mRNA Decay: Degradation of Defective Transcripts Is Only Part of the Story.
abstract: Nonsense-mediated mRNA decay (NMD) is a eukaryotic surveillance mechanism that monitors cytoplasmic mRNA translation and targets mRNAs undergoing premature translation termination for rapid degradation. From yeasts to humans, activation of NMD requires the function of the three conserved Upf factors: Upf1, Upf2, and Upf3. Here, we summarize the progress in our understanding of the molecular mechanisms of NMD in several model systems and discuss recent experiments that address the roles of Upf1, the principal regulator of NMD, in the initial targeting and final degradation of NMD-susceptible mRNAs. We propose a unified model for NMD in which the Upf factors provide several functions during premature termination, including the stimulation of release factor activity and the dissociation and recycling of ribosomal subunits. In this model, the ultimate degradation of the mRNA is the last step in a complex premature termination process.
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts 01655; email: feng.he@umassmed.edu , allan.jacobson@umassmed.edu.
authors.forename: Feng
authors.initials: F
authors.lastname: He
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts 01655; email: feng.he@umassmed.edu , allan.jacobson@umassmed.edu.
authors.forename: Allan
authors.initials: A
authors.lastname: Jacobson
mesh_terms: D000818:Animals; D006801:Humans; D008322:Mammals; D059365:Nonsense Mediated mRNA Decay / Q000502:physiology*; D010443:Peptide Chain Termination, Translational; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D020365:RNA Helicases; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D020365:RNA Helicases; D016601:RNA-Binding Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C468286:UPF2 protein, human; C435487:UPF3A protein, human; C514704:SMG1 protein, human; C101828:UPF1 protein, human
keywords: Upf proteins; quality control; ribosome dissociation; translation termination