title: Quality control of transcription start site selection by nonsense-mediated-mRNA decay.
abstract: Nonsense-mediated mRNA decay (NMD) is a translation-dependent RNA quality-control pathway targeting transcripts such as messenger RNAs harboring premature stop-codons or short upstream open reading frame (uORFs). Our transcription start sites (TSSs) analysis of Saccharomyces cerevisiae cells deficient for RNA degradation pathways revealed that about half of the pervasive transcripts are degraded by NMD, which provides a fail-safe mechanism to remove spurious transcripts that escaped degradation in the nucleus. Moreover, we found that the low specificity of RNA polymerase II TSSs selection generates, for 47% of the expressed genes, NMD-sensitive transcript isoforms carrying uORFs or starting downstream of the ATG START codon. Despite the low abundance of this last category of isoforms, their presence seems to constrain genomic sequences, as suggested by the significant bias against in-frame ATGs specifically found at the beginning of the corresponding genes and reflected by a depletion of methionines in the N-terminus of the encoded proteins.
authors.affiliation: Institut Pasteur, UMR3525, Génétique des Interactions Macromoléculaires, Centre National de la Recherche Scientifique, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Malabat
authors.affiliation: Institut Pasteur, UMR3525, Génétique des Interactions Macromoléculaires, Centre National de la Recherche Scientifique, Paris, France.
authors.forename: Frank
authors.initials: F
authors.lastname: Feuerbach
authors.affiliation: Plate-Forme Génomique, Institut Pasteur, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Ma
authors.affiliation: Institut Pasteur, UMR3525, Génétique des Interactions Macromoléculaires, Centre National de la Recherche Scientifique, Paris, France.
authors.forename: Cosmin
authors.initials: C
authors.lastname: Saveanu
authors.affiliation: Institut Pasteur, UMR3525, Génétique des Interactions Macromoléculaires, Centre National de la Recherche Scientifique, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Jacquier
mesh_terms: D018389:Codon, Nonsense; D015966:Gene Expression Regulation, Fungal; D059365:Nonsense Mediated mRNA Decay; D016366:Open Reading Frames; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism; D012331:RNA, Fungal / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D024363:Transcription Initiation Site
chemical_list: D018389:Codon, Nonsense; D012331:RNA, Fungal; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D012319:RNA Polymerase II
keywords: RNA quality control; S. cerevisiae; chromosomes; evolutionary biology; genes; genomics; non-coding RNAs; non-sense mediated mRNA decay; nuclear RNA degradation; transcription initiation