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

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Abstract

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.

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Acknowledgments

The research of the authors is supported by grants from the European Research Council, the Swiss National Science Foundation, the Novartis Foundation for Biomedical Research, the Helmut Horten Foundation and also by the Kanton Bern. O.M. is a fellow of the Max Cloëtta Foundation and R.Z.O. is supported by a fellowship from CONACYT México.

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  1. Institute of Cell Biology, University of Bern, Baltzerstrasse 4, 3012, Bern, Switzerland

    Pamela Nicholson, Hasmik Yepiskoposyan, Stefanie Metze, Rodolfo Zamudio Orozco, Nicole Kleinschmidt & Oliver Mühlemann

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  1. Pamela Nicholson
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  2. Hasmik Yepiskoposyan
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  3. Stefanie Metze
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  4. Rodolfo Zamudio Orozco
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  5. Nicole Kleinschmidt
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  6. Oliver Mühlemann
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Correspondence to Oliver Mühlemann.

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Nicholson, P., Yepiskoposyan, H., Metze, S. et al. Nonsense-mediated mRNA decay in human cells: mechanistic insights, functions beyond quality control and the double-life of NMD factors. Cell. Mol. Life Sci. 67, 677–700 (2010). https://doi.org/10.1007/s00018-009-0177-1

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  • DOI: https://doi.org/10.1007/s00018-009-0177-1

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