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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.

SUBMITTER: Celik A 

PROVIDER: S-EPMC5393182 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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High-resolution profiling of NMD targets in yeast reveals translational fidelity as a basis for substrate selection.

Celik Alper A   Baker Richard R   He Feng F   Jacobson Allan A  

RNA (New York, N.Y.) 20170216 5


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 <i>UPF1</i>, <i>UPF2</i>, or <i>UPF3</i> genes. Our new RNA-seq analyses confirm previous results of microarray studies, but also uncover hundreds of new NMD-regulated transcripts that had esc  ...[more]

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