Nonsense‐mediated RNA decay – a switch and dial for regulating gene expression

• Published in: BioEssays Vol. 37; no. 6; pp. 612 - 623
• Main Authors: Smith, Jenna E, Baker, Kristian E
• Format: Journal Article
• Language: English
• Published: United States Published for ICSU Press by Cambridge University Press 01.06.2015; Blackwell Publishing Ltd; Wiley Subscription Services, Inc
• Subjects: Animals; autoregulation; biogenesis; Cell Nucleus - metabolism; Decay; Epigenesis, Genetic; Gene expression; gene regulation; genes; Humans; messenger RNA; mutation; noncoding RNA; Nonsense Mediated mRNA Decay; nonsense-mediated RNA decay; Protein Biosynthesis; Quality control; RNA Precursors - genetics; RNA Precursors - metabolism; RNA Splicing; transcriptome; translation (genetics); translation termination; translation termination; noncoding RNA; quality control; gene regulation; nonsense-mediated RNA decay
• ISSN: 0265-9247; 1521-1878
• DOI: 10.1002/bies.201500007

Nonsense‐mediated RNA decay (NMD) represents an established quality control checkpoint for gene expression that protects cells from consequences of gene mutations and errors during RNA biogenesis that lead to premature termination during translation. Characterization of NMD‐sensitive transcriptomes has revealed, however, that NMD targets not only aberrant transcripts but also a broad array of mRNA isoforms expressed from many endogenous genes. NMD is thus emerging as a master regulator that drives both fine and coarse adjustments in steady‐state RNA levels in the cell. Importantly, while NMD activity is subject to autoregulation as a means to maintain homeostasis, modulation of the pathway by external cues provides a means to reprogram gene expression and drive important biological processes. Finally, the unanticipated observation that transcripts predicted to lack protein‐coding capacity are also sensitive to this translation‐dependent surveillance mechanism implicates NMD in regulating RNA function in new and diverse ways.