1. Biochemistry and Chemical Biology
  2. Genetics and Genomics
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The long non-coding RNA Cerox1 is a post transcriptional regulator of mitochondrial complex I catalytic activity

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Cite this article as: eLife 2019;8:e45051 doi: 10.7554/eLife.45051

Abstract

To generate energy efficiently, the cell is uniquely challenged to co-ordinate the abundance of electron transport chain protein subunits expressed from both nuclear and mitochondrial genomes. How an effective stoichiometry of this many constituent subunits is co-ordinated post-transcriptionally remains poorly understood. Here we show that Cerox1, an unusually abundant cytoplasmic long noncoding RNA (lncRNA), modulates the levels of mitochondrial complex I subunit transcripts in a manner that requires binding to microRNA-488-3p. Increased abundance of Cerox1 cooperatively elevates complex I subunit protein abundance and enzymatic activity, decreases reactive oxygen species production, and protects against the complex I inhibitor rotenone. Cerox1 function is conserved across placental mammals: human and mouse orthologues effectively modulate complex I enzymatic activity in mouse and human cells, respectively. Cerox1 is the first lncRNA demonstrated, to our knowledge, to regulate mitochondrial oxidative phosphorylation and, with miR-488-3p, represent novel targets for the modulation of complex I activity.

Article and author information

Author details

  1. Tamara M Sirey

    MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom
    For correspondence
    tamara.sirey@igmm.ed.ac.uk
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5606-2858
  2. Kenny Roberts

    MRC Functional Genomics Unit, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6155-0821
  3. Wilfried Haerty

    MRC Functional Genomics Unit, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  4. Oscar Bedoya-Reina

    MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    No competing interests declared.
  5. Sebastian Rogatti-Granados

    MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    No competing interests declared.
  6. Jennifer Y Tan

    MRC Functional Genomics Unit, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  7. Nick Li

    MRC Functional Genomics Unit, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  8. Lisa C Heather

    Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  9. Roderick N Carter

    British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    No competing interests declared.
  10. Sarah Cooper

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  11. Andrew J Finch

    MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8065-4623
  12. Jimi Wills

    MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    No competing interests declared.
  13. Nicholas M Morton

    British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    No competing interests declared.
  14. Ana Claudia Marques

    MRC Functional Genomics Unit, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5174-8092
  15. Chris P Ponting

    MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom
    For correspondence
    Chris.Ponting@igmm.ed.ac.uk
    Competing interests
    Chris P Ponting, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0202-7816

Funding

Wellcome (WT106956/Z/15/Z)

  • Tamara M Sirey
  • Oscar Bedoya-Reina
  • Sebastian Rogatti-Granados
  • Chris P Ponting

European Research Council (249869)

  • Tamara M Sirey
  • Kenny Roberts
  • Ana Claudia Marques
  • Chris P Ponting

Wellcome (WT100981/z/13/z)

  • Roderick N Carter
  • Nicholas M Morton

Medical Research Council

  • Wilfried Haerty
  • Chris P Ponting

Diabetes UK

  • Lisa C Heather

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

Reviewing Editor

  1. Detlef Weigel, Max Planck Institute for Developmental Biology, Germany

Publication history

  1. Received: January 10, 2019
  2. Accepted: May 2, 2019
  3. Accepted Manuscript published: May 2, 2019 (version 1)

Copyright

© 2019, Sirey 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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