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Kinetochore inactivation by expression of a repressive mRNA

  1. Jingxun Chen
  2. Amy Tresenrider
  3. Minghao Chia
  4. David T McSwiggen
  5. Gianpiero Spedale
  6. Victoria Jorgensen
  7. Hanna Liao
  8. Folkert Jacobus van Werven Is a corresponding author
  9. Elcin Unal Is a corresponding author
  1. University of California, Berkeley, United States
  2. The Francis Crick Institute, United Kingdom
  3. Li Ka Shing Center, University of California, United States
  4. University of California, United States
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Cite as: eLife 2017;6:e27417 doi: 10.7554/eLife.27417

Abstract

Differentiation programs such as meiosis depend on extensive gene regulation to mediate cellular morphogenesis. Meiosis requires transient removal of the outer kinetochore, the complex that connects microtubules to chromosomes. How the meiotic gene expression program temporally restricts kinetochore function is unknown. We discovered that in budding yeast, kinetochore inactivation occurs by reducing the abundance of a limiting subunit, Ndc80. Furthermore, we uncovered an integrated mechanism that acts at the transcriptional and translational level to repress NDC80 expression. Central to this mechanism is the developmentally controlled transcription of an alternate NDC80 mRNA isoform, which itself cannot produce protein due to regulatory upstream ORFs in its extended 5' leader. Instead, transcription of this isoform represses the canonical NDC80 mRNA expression in cis, thereby inhibiting Ndc80 protein synthesis. This model of gene regulation raises the intriguing notion that transcription of an mRNA, despite carrying a canonical coding sequence, can directly cause gene repression.

Article and author information

Author details

  1. Jingxun Chen

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Amy Tresenrider

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Minghao Chia

    The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. David T McSwiggen

    Department of Molecular and Cell Biology, Li Ka Shing Center, University of California, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Gianpiero Spedale

    The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Victoria Jorgensen

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Hanna Liao

    Department of Molecular and Cell Biology, University of California, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Folkert Jacobus van Werven

    The Francis Crick Institute, London, United Kingdom
    For correspondence
    folkert.vanwerven@crick.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0002-6685-2084
  9. Elcin Unal

    Department of Molecular and Cell Biology, University of California, Berkeley, United States
    For correspondence
    elcin@berkeley.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0002-6768-609X

Funding

March of Dimes Foundation (5-FY15-99)

  • Elcin Unal

Pew Charitable Trusts (27344)

  • Elcin Unal

Glenn Foundation for Medical Research

  • Elcin Unal

Francis Crick Institute

  • Folkert Jacobus van Werven

National Science Foundation

  • Jingxun Chen

Agency for Science, Technology and Research

  • Minghao Chia

Damon Runyon Cancer Research Foundation (35-15)

  • Elcin Unal

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

Reviewing Editor

  1. Scott Keeney, Reviewing Editor, Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, United States

Publication history

  1. Received: April 3, 2017
  2. Accepted: September 1, 2017
  3. Accepted Manuscript published: September 14, 2017 (version 1)

Copyright

© 2017, Chen 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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