Journal
ANNUAL REVIEW OF GENETICS, VOL 49
Volume 49, Issue -, Pages 339-366Publisher
ANNUAL REVIEWS
DOI: 10.1146/annurev-genet-112414-054639
Keywords
quality control; Upf proteins; translation termination; ribosome dissociation
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Funding
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM027757, R37GM027757] Funding Source: NIH RePORTER
- NIGMS NIH HHS [R37 GM027757, R01 GM027757, R37GM27757] Funding Source: Medline
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Nonsense-mediated mRNA decay(NMD) is a eukaryotic surveillance mechanism that monitors cytoplasmic mRNA translation and targets mRNAs undergoing premature translation termination for rapid degradation. From yeasts to humans, activation of NMD requires the function of the three conserved Upf factors: Upf1, Upf2, and Upf3. Here, we summarize the progress in our understanding of the molecular mechanisms of NMD in several model systems and discuss recent experiments that address the roles of Upf1, the principal regulator of NMD, in the initial targeting and final degradation of NMD-susceptible mRNAs. We propose a unified model for NMD in which the Upf factors provide several functions during premature termination, including the stimulation of release factor activity and the dissociation and recycling of ribosomal subunits. In this model, the ultimate degradation of the mRNA is the last step in a complex premature termination process.
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