1. Biochemistry and Chemical Biology
  2. Computational and Systems Biology
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Deep transcriptome annotation enables the discovery and functional characterization of cryptic small proteins

Research Article
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Cite this article as: eLife 2017;6:e27860 doi: 10.7554/eLife.27860

Abstract

Recent functional, proteomic and ribosome profiling studies in eukaryotes have concurrently demonstrated the translation of alternative open reading frames (altORFs) in addition to annotated protein coding sequences (CDSs). We show that a large number of small proteins could in fact be coded by these altORFs. The putative alternative proteins translated from altORFs have orthologs in many species and contain functional domains. Evolutionary analyses indicate that altORFs often show more extreme conservation patterns than their CDSs. Thousands of alternative proteins are detected in proteomic datasets by reanalysis using a database containing predicted alternative proteins. This is illustrated with specific examples, including altMiD51, a 70 amino acid mitochondrial fission-promoting protein encoded in MiD51/Mief1/SMCR7L, a gene encoding an annotated protein promoting mitochondrial fission. Our results suggest that many genes are multicoding genes and code for a large protein and one or several small proteins.

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Article and author information

Author details

  1. Sondos Samandi

    Department of Biochemistry, Université de Sherbrooke, Sherbrooke, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. Annie V Roy

    Department of Biochemistry, Université de Sherbrooke, Sherbrooke, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Vivian Delcourt

    Department of Biochemistry, Université de Sherbrooke, Sherbrooke, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. Jean-François Lucier

    Department of Biology, Université de Sherbrooke, Sherbrooke, Canada
    Competing interests
    The authors declare that no competing interests exist.
  5. Jules Gagnon

    Department of Biology, Université de Sherbrooke, Sherbrooke, Canada
    Competing interests
    The authors declare that no competing interests exist.
  6. Maxime C Beaudoin

    Department of Biochemistry, Université de Sherbrooke, Sherbrooke, Canada
    Competing interests
    The authors declare that no competing interests exist.
  7. Benoît Vanderperre

    Department of Biochemistry, Université de Sherbrooke, Sherbrooke, Canada
    Competing interests
    The authors declare that no competing interests exist.
  8. Marc-André Breton

    Department of Biochemistry, Université de Sherbrooke, Sherbrooke, Canada
    Competing interests
    The authors declare that no competing interests exist.
  9. Julie Motard

    Department of Biochemistry, Université de Sherbrooke, Sherbrooke, Canada
    Competing interests
    The authors declare that no competing interests exist.
  10. Jean-François Jacques

    Department of Biochemistry, Université de Sherbrooke, Sherbrooke, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0465-0313
  11. Mylène Brunelle

    Department of Biochemistry, Université de Sherbrooke, Sherbrooke, Canada
    Competing interests
    The authors declare that no competing interests exist.
  12. Isabelle Gagnon-Arsenault

    Département de biologie, Université Laval, Quebec, Canada
    Competing interests
    The authors declare that no competing interests exist.
  13. Isabelle Fournier

    Prism INSERM U1192, Université de Lille, Lille, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1096-5044
  14. Aïda Ouangraoua

    Department of Computer Science, Université de Sherbrooke, Sherbrooke, Canada
    Competing interests
    The authors declare that no competing interests exist.
  15. Darel J Hunting

    Department of Nuclear Medicine and Radiobiology, Université de Sherbrooke, Sherbrooke, Canada
    Competing interests
    The authors declare that no competing interests exist.
  16. Alan A Cohen

    Department of Family Medicine, Université de Sherbrooke, Sherbrooke, Canada
    Competing interests
    The authors declare that no competing interests exist.
  17. Christian R Landry

    Département de biologie, Université Laval, Quebec, Canada
    Competing interests
    The authors declare that no competing interests exist.
  18. Michelle S Scott

    Department of Biochemistry, Université de Sherbrooke, Sherbrooke, Canada
    Competing interests
    The authors declare that no competing interests exist.
  19. Xavier Roucou

    Department of Biochemistry, Université de Sherbrooke, Sherbrooke, Canada
    For correspondence
    xavier.roucou@usherbrooke.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9370-5584

Funding

Canadian Institutes of Health Research (MOP-137056)

  • Xavier Roucou

Canada Research Chairs

  • Aïda Ouangraoua
  • Christian R Landry
  • Xavier Roucou

Fonds de Recherche du Québec - Nature et Technologies (2015-PR-181807)

  • Christian R Landry
  • Xavier Roucou

Merck Sharp and Dohme

  • Xavier Roucou

Canadian Institutes of Health Research (MOP-136962)

  • Xavier Roucou

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Nir Ben-Tal, Tel Aviv University, Israel

Publication history

  1. Received: April 17, 2017
  2. Accepted: October 29, 2017
  3. Accepted Manuscript published: October 30, 2017 (version 1)
  4. Version of Record published: November 27, 2017 (version 2)

Copyright

© 2017, Samandi 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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Further reading

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