High-resolution profiling of NMD targets in yeast reveals translational fidelity as a basis for substrate selection
- PMID: 28209632
- PMCID: PMC5393182
- DOI: 10.1261/rna.060541.116
High-resolution profiling of NMD targets in yeast reveals translational fidelity as a basis for substrate selection
Abstract
Nonsense-mediated mRNA decay (NMD) plays an important role in eukaryotic gene expression, yet the scope and the defining features of NMD-targeted transcripts remain elusive. To address these issues, we reevaluated the genome-wide expression of annotated transcripts in yeast cells harboring deletions of the UPF1, UPF2, or UPF3 genes. Our new RNA-seq analyses confirm previous results of microarray studies, but also uncover hundreds of new NMD-regulated transcripts that had escaped previous detection, including many intron-containing pre-mRNAs and several noncoding RNAs. The vast majority of NMD-regulated transcripts are normal-looking protein-coding mRNAs. Our bioinformatics analyses reveal that this set of NMD-regulated transcripts generally have lower translational efficiency and higher ratios of out-of-frame translation. NMD-regulated transcripts also have lower average codon optimality scores and higher transition probability to nonoptimal codons. Collectively, our results generate a comprehensive catalog of yeast NMD substrates and yield new insights into the mechanisms by which these transcripts are targeted by NMD.
Keywords: NMD substrates; codon optimality; translational fidelity and efficiency.
© 2017 Celik et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.
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