Nonsense-mediated mRNA decay in human cells: mechanistic insights, functions beyond quality control and the double-life of NMD factors

Nonsense-mediated decay is well known by the lucid definition of being a RNA surveillance mechanism that ensures the speedy degradation of mRNAs containing premature translation termination codons. However, as we review here, NMD is far from being a simple quality control mechanism; it also regulate...

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Bibliographic Details
Published in:Cellular and molecular life sciences : CMLS 2010-03, Vol.67 (5), p.677-700
Main Authors: Nicholson, Pamela, Yepiskoposyan, Hasmik, Metze, Stefanie, Zamudio Orozco, Rodolfo, Kleinschmidt, Nicole, Mühlemann, Oliver
Format: Article
Language:English
Subjects:
Biochemistry
Biomechanical Phenomena
Biomedical and Life Sciences
Biomedicine
Cell Biology
Cells - metabolism
Cellular biology
Codon, Nonsense - metabolism
Decay
Disease - etiology
Disease - genetics
Gene expression
Humans
Life Sciences
Models, Biological
Protein synthesis
Quality Control
Review
Ribonucleic acid
RNA
RNA Processing, Post-Transcriptional - physiology
RNA Stability - genetics
RNA Stability - physiology
Trans-Activators - genetics
Trans-Activators - metabolism
Trans-Activators - physiology
Transcription Factors - metabolism
Transcription Factors - physiology
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Summary:Nonsense-mediated decay is well known by the lucid definition of being a RNA surveillance mechanism that ensures the speedy degradation of mRNAs containing premature translation termination codons. However, as we review here, NMD is far from being a simple quality control mechanism; it also regulates the stability of many wild-type transcripts. We summarise the abundance of research that has characterised each of the NMD factors and present a unified model for the recognition of NMD substrates. The contentious issue of how and where NMD occurs is also discussed, particularly with regard to P-bodies and SMG6-driven endonucleolytic degradation. In recent years, the discovery of additional functions played by several of the NMD factors has further complicated the picture. Therefore, we also review the reported roles of UPF1, SMG1 and SMG6 in other cellular processes.
ISSN:1420-682X
1420-9071
DOI:10.1007/s00018-009-0177-1