Nonsense-Mediated mRNA Decay Begins Where Translation Ends

Nonsense-mediated mRNA decay (NMD) is arguably the best-studied eukaryotic messenger RNA (mRNA) surveillance pathway, yet fundamental questions concerning the molecular mechanism of target RNA selection remain unsolved. Besides degrading defective mRNAs harboring premature termination codons (PTCs),...

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Bibliographic Details
Published in:Cold Spring Harbor perspectives in biology 2019-02, Vol.11 (2)
Main Authors: Karousis, Evangelos D, Mühlemann, Oliver
Format: Article
Language:English
Subjects:
Activation
Biological activity
Codon, Nonsense
Codons
Decay
Eukaryota
Gene expression
Homeostasis
mRNA turnover
Nonsense Mediated mRNA Decay
Peptide Chain Termination, Translational
PERSPECTIVES
Protein Biosynthesis
Proteins
Ribonucleic acid
RNA
RNA, Messenger - genetics
RNA, Messenger - metabolism
Target recognition
Translation
Translation termination
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Summary:Nonsense-mediated mRNA decay (NMD) is arguably the best-studied eukaryotic messenger RNA (mRNA) surveillance pathway, yet fundamental questions concerning the molecular mechanism of target RNA selection remain unsolved. Besides degrading defective mRNAs harboring premature termination codons (PTCs), NMD also targets many mRNAs encoding functional full-length proteins. Thus, NMD impacts on a cell's transcriptome and is implicated in a range of biological processes that affect a broad spectrum of cellular homeostasis. Here, we focus on the steps involved in the recognition of NMD targets and the activation of NMD. We summarize the accumulating evidence that tightly links NMD to translation termination and we further discuss the recruitment and activation of the mRNA degradation machinery and the regulation of this complex series of events. Finally, we review emerging ideas concerning the mechanistic details of NMD activation and the potential role of NMD as a general surveyor of translation efficacy.
ISSN:1943-0264
DOI:10.1101/cshperspect.a032862