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Review
. 2014 Sep;13(9):1126-35.
doi: 10.1128/EC.00090-14. Epub 2014 Jul 18.

Regulation of natural mRNAs by the nonsense-mediated mRNA decay pathway

Megan Peccarelli  1 , Bessie W Kebaara  2
Affiliations
Review

Regulation of natural mRNAs by the nonsense-mediated mRNA decay pathway

Megan Peccarelli et al. Eukaryot Cell. 2014 Sep.

Abstract

The nonsense-mediated mRNA decay (NMD) pathway is a specialized mRNA degradation pathway that degrades select mRNAs. This pathway is conserved in all eukaryotes examined so far, and it triggers the degradation of mRNAs that prematurely terminate translation. Originally identified as a pathway that degrades mRNAs with premature termination codons as a result of errors during transcription, splicing, or damage to the mRNA, NMD is now also recognized as a pathway that degrades some natural mRNAs. The degradation of natural mRNAs by NMD has been identified in multiple eukaryotes, including Saccharomyces cerevisiae, Drosophila melanogaster, Arabidopsis thaliana, and humans. S. cerevisiae is used extensively as a model to study natural mRNA regulation by NMD. Inactivation of the NMD pathway in S. cerevisiae affects approximately 10% of the transcriptome. Similar percentages of natural mRNAs in the D. melanogaster and human transcriptomes are also sensitive to the pathway, indicating that NMD is important for the regulation of gene expression in multiple organisms. NMD can either directly or indirectly regulate the decay rate of natural mRNAs. Direct NMD targets possess NMD-inducing features. This minireview focuses on the regulation of natural mRNAs by the NMD pathway, as well as the features demonstrated to target these mRNAs for decay by the pathway in S. cerevisiae. We also compare NMD-targeting features identified in S. cerevisiae with known NMD-targeting features in other eukaryotic organisms.

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Figures

FIG 1
FIG 1
Schematic representation of NMD-targeting features in S. cerevisiae. (A) Intron containing pre-mRNA containing a stop codon. (B) mRNA with an atypically long 3′ UTR. (C) mRNA with an upstream open reading frame (uORF) in the 5′ UTR that can induce NMD. (D) mRNAs with sequence features that can induce a −1 ribosomal frameshift. (E) mRNA with a suboptimal start codon context that may be subject to out-of-frame translation initiation in an alternate AUG codon within the ORF, which can lead to a PTC and NMD activation. ORFs are illustrated by thick orange lines, and untranslated regions (UTRs) and introns are shown by thin green lines. The poly(A) tail is shown in blue, and ribosomes are illustrated in gray. AUG, start codon; PTC, premature termination codon; PRF, programmed (−1) ribosomal frameshift; PAB1P, poly(A)-binding protein.
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