Physiological and pathophysiological role of nonsense-mediated mRNA decay

Nonsense-mediated messenger RNA (mRNA) decay (NMD) is a quality control mechanism that degrades irregular or faulty mRNAs. NMD mainly degrades mRNAs, which contain a premature termination codon (PTC) and therefore encode a truncated protein. Furthermore, NMD alters the expression of different types of cellular mRNAs, the so-called endogenous NMD substrates. In this review, we focus on the impact of NMD on cellular and molecular physiology. We specify key classes of NMD substrates and provide a detailed overview of the physiological function of gene regulation by NMD. We also describe different mechanisms of NMD substrate degradation and how the regulation of the NMD machinery affects cellular physiology. Finally, we outline the physiological functions of central NMD factors.