title: Translation of small open reading frames within unannotated RNA transcripts in Saccharomyces cerevisiae.
abstract: High-throughput gene expression analysis has revealed a plethora of previously undetected transcripts in eukaryotic cells. In this study, we investigate >1,100 unannotated transcripts in yeast predicted to lack protein-coding capacity. We show that a majority of these RNAs are enriched on polyribosomes akin to mRNAs. Ribosome profiling demonstrates that many bind translocating ribosomes within predicted open reading frames 10-96 codons in size. We validate expression of peptides encoded within a subset of these RNAs and provide evidence for conservation among yeast species. Consistent with their translation, many of these transcripts are targeted for degradation by the translation-dependent nonsense-mediated RNA decay (NMD) pathway. We identify lncRNAs that are also sensitive to NMD, indicating that translation of noncoding transcripts also occurs in mammals. These data demonstrate transcripts considered to lack coding potential are bona fide protein coding and expand the proteome of yeast and possibly other eukaryotes.
authors.affiliation: Center for RNA Molecular Biology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Jenna E
authors.initials: JE
authors.lastname: Smith
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
authors.forename: Juan R
authors.initials: JR
authors.lastname: Alvarez-Dominguez
authors.affiliation: Center for RNA Molecular Biology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Kline
authors.affiliation: Center for RNA Molecular Biology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Huynh
authors.affiliation: Center for RNA Molecular Biology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Geisler
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
authors.forename: Wenqian
authors.initials: W
authors.lastname: Hu
authors.affiliation: Center for RNA Molecular Biology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Jeff
authors.initials: J
authors.lastname: Coller
authors.affiliation: Center for RNA Molecular Biology, Case Western Reserve University, Cleveland, OH 44106, USA. Electronic address: keb22@case.edu.
authors.forename: Kristian E
authors.initials: KE
authors.lastname: Baker
mesh_terms: D000818:Animals; D015966:Gene Expression Regulation, Fungal; D016366:Open Reading Frames; D011132:Polyribosomes / Q000378:metabolism*; D014176:Protein Biosynthesis; D020871:RNA Stability; D012331:RNA, Fungal / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D012331:RNA, Fungal; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins