1. Chromosomes and Gene Expression
  2. Genetics and Genomics
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Quality control of transcription start site selection by Nonsense-Mediated-mRNA Decay

  1. Christophe Malabat
  2. Frank Feuerbach
  3. Laurence Ma
  4. Cosmin Saveanu
  5. Alain Jacquier  Is a corresponding author
  1. Centre National de la Recherche Scientifique, France
  2. Institut Pasteur, France
Research Article
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Cite this article as: eLife 2015;4:e06722 doi: 10.7554/eLife.06722

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.

Article and author information

Author details

  1. Christophe Malabat

    Institut Pasteur, UMR3525, Génétique des Interactions Macromoléculaires, Centre National de la Recherche Scientifique, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Frank Feuerbach

    Institut Pasteur, UMR3525, Génétique des Interactions Macromoléculaires, Centre National de la Recherche Scientifique, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Laurence Ma

    Plate-Forme Génomique, Institut Pasteur, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Cosmin Saveanu

    Institut Pasteur, UMR3525, Génétique des Interactions Macromoléculaires, Centre National de la Recherche Scientifique, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Alain Jacquier

    Institut Pasteur, UMR3525, Génétique des Interactions Macromoléculaires, Centre National de la Recherche Scientifique, Paris, France
    For correspondence
    alain.jacquier@pasteur.fr
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Torben Heick Jensen, Aarhus University, Denmark

Publication history

  1. Received: January 27, 2015
  2. Accepted: April 22, 2015
  3. Accepted Manuscript published: April 23, 2015 (version 1)
  4. Version of Record published: May 18, 2015 (version 2)

Copyright

© 2015, Malabat et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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