title: 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 theUPF1,UPF2, orUPF3genes. 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.
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
authors.forename: Alper
authors.initials: A
authors.lastname: Celik
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Baker
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: He
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
authors.forename: Allan
authors.initials: A
authors.lastname: Jacobson
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D003062:Codon; D005095:Exoribonucleases / Q000378:metabolism; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D007438:Introns; D059365:Nonsense Mediated mRNA Decay; D014176:Protein Biosynthesis; D020365:RNA Helicases / Q000235:genetics; D012322:RNA Precursors / Q000737:chemistry; D012331:RNA, Fungal / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D059467:Transcriptome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003062:Codon; C092470:NMD2 protein, S cerevisiae; D012322:RNA Precursors; D012331:RNA, Fungal; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; C096360:UPF3 protein, S cerevisiae; D005095:Exoribonucleases; C074151:NAM7 protein, S cerevisiae; D020365:RNA Helicases
keywords: NMD substrates; codon optimality; translational fidelity and efficiency