Control of gene expression through the nonsense-mediated RNA decay pathway

Abstract

Nonsense-mediated RNA decay (NMD) was originally discovered as a cellular surveillance pathway that safeguards the quality of mRNA transcripts in eukaryotic cells. In its canonical function, NMD prevents translation of mutant mRNAs harboring premature termination codons (PTCs) by targeting them for degradation. However, recent studies have shown that NMD has a much broader role in gene expression by regulating the stability of many normal transcripts. In this review, we discuss the function of NMD in normal physiological processes, its dynamic regulation by developmental and environmental cues, and its association with human disease.

Keywords: Gene expression; Human disease; Nonsense-mediated decay; RNA surveillance.

Fig. 1

NMD functions both in RNA surveillance and in gene regulation. Several features of mRNA transcripts can mark the transcripts as substrates for degradation by NMD. Green boxes, exons; lines, introns; potential splicing events are shown by blue or purple lines; genetic mutations and transcriptional aberrations are denoted with stars. The translation start site (ATG) is marked by arrows and stop codons are marked by red circles