Journal
BIOESSAYS
Volume 37, Issue 6, Pages 612-623Publisher
WILEY
DOI: 10.1002/bies.201500007
Keywords
gene regulation; noncoding RNA; nonsense-mediated RNA decay; quality control; translation termination
Categories
Funding
- National Institutes of Health [GM095621]
- National Science Foundation [MCB1253788]
- NIH [T32 GM008056]
- Div Of Molecular and Cellular Bioscience
- Direct For Biological Sciences [1253788] Funding Source: National Science Foundation
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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.
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