Cellular and Molecular Life Sciences

, Volume 72, Issue 23, pp 4523–4544 | Cite as

Mechanism, factors, and physiological role of nonsense-mediated mRNA decay

Review

Abstract

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.

Keywords

NMD Quality control UPF1 Exon junction complex Genetic disease 

Notes

Acknowledgments

This research was funded by grants from the Fritz Thyssen Stiftung and the Deutsche Forschungsgemeinschaft (SFB635, project B06) to N.H.G.

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Copyright information

© Springer Basel 2015

Authors and Affiliations

  1. 1.Institute for GeneticsUniversity of CologneCologneGermany

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