Mechanism, factors, and physiological role of nonsense-mediated mRNA decay.
Nonsense-mediated mRNA decay (NMD) is a translation-dependent, multistep process that degrades irregular or faulty messenger RNAs (mRNAs). NMD mainly targets mRNAs with a truncated open reading frame (ORF) due to premature termination codons (PTCs). In addition, NMD also regulates the expression of different types of endogenous mRNA substrates. A multitude of factors are involved in the tight regulation of the NMD mechanism. In this review, we focus on the molecular mechanism of mammalian NMD. Based on the published data, we discuss the involvement of translation termination in NMD initiation. Furthermore, we provide a detailed overview of the core NMD machinery, as well as several peripheral NMD factors, and discuss their function. Finally, we present an overview of diseases associated with NMD factor mutations and summarize the current state of treatment for genetic disorders caused by nonsense mutations.
Institute for Genetics, University of Cologne, Cologne, Germany.
Tobias
T
Fatscher
Institute for Genetics, University of Cologne, Cologne, Germany.
Volker
V
Boehm
Institute for Genetics, University of Cologne, Cologne, Germany. ngehring@uni-koeln.de.
Niels H
http://orcid.org/0000-0001-7792-1164
NH
Gehring
D020413:3' Untranslated Regions; D000818:Animals; D018389:Codon, Nonsense; D053487:DEAD-box RNA Helicases / Q000235:genetics; D039601:Eukaryotic Initiation Factor-4A / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D038901:X-Linked Intellectual Disability / Q000235:genetics; D009154:Mutation; D059365:Nonsense Mediated mRNA Decay / Q000502:physiology*; D010443:Peptide Chain Termination, Translational / Q000502:physiology; D010766:Phosphorylation; D020365:RNA Helicases; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D004722:Endoribonucleases
D020413:3' Untranslated Regions; D018389:Codon, Nonsense; D053487:DEAD-box RNA Helicases; D039601:Eukaryotic Initiation Factor-4A; D020365:RNA Helicases; D016601:RNA-Binding Proteins; D019098:Telomerase; D015534:Trans-Activators; D014157:Transcription Factors; C406243:RBM8A protein, human; C468286:UPF2 protein, human; C435487:UPF3A protein, human; C512261:SMG6 protein, human; D004722:Endoribonucleases; C403493:EIF4A3 protein, human; C101828:UPF1 protein, human
Exon junction complex; Genetic disease; NMD; Quality control; UPF1