A microtranslatome coordinately regulates sodium and potassium currents in the human heart

  1. Catherine A Eichel
  2. Erick B Rios-Pérez
  3. Fang Liu
  4. Margaret B Jameson
  5. David K Jones
  6. Jennifer J Knickelbine
  7. Gail A Robertson  Is a corresponding author
  1. University of Wisconsin School of Medicine and Public Health, United States

Abstract

Catastrophic arrhythmias and sudden cardiac death can occur with even a small imbalance between inward sodium currents and outward potassium currents, but mechanisms establishing this critical balance are not understood. Here, we show that mRNA transcripts encoding INa and IKr channels (SCN5A and hERG, respectively) are associated in defined complexes during protein translation. Using biochemical, electrophysiological and single-molecule fluorescence localization approaches, we find that roughly half the hERG translational complexes contain SCN5A transcripts. Moreover, the transcripts are regulated in a way that alters functional expression of both channels at the membrane. Association and coordinate regulation of transcripts in discrete 'microtranslatomes' represents a new paradigm controlling electrical activity in heart and other excitable tissues.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for all figures.

Article and author information

Author details

  1. Catherine A Eichel

    Department of Neuroscience, University of Wisconsin School of Medicine and Public Health, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Erick B Rios-Pérez

    Department of Neuroscience, University of Wisconsin School of Medicine and Public Health, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Fang Liu

    Department of Neuroscience, University of Wisconsin School of Medicine and Public Health, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Margaret B Jameson

    Department of Neuroscience, University of Wisconsin School of Medicine and Public Health, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1225-9194
  5. David K Jones

    Department of Neuroscience, University of Wisconsin School of Medicine and Public Health, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Jennifer J Knickelbine

    Department of Neuroscience, University of Wisconsin School of Medicine and Public Health, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Gail A Robertson

    Department of Neuroscience, University of Wisconsin School of Medicine and Public Health, Madison, United States
    For correspondence
    garobert@wisc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4694-5790

Funding

National Heart, Lung, and Blood Institute (1R01HL131403-01A1)

  • Gail A Robertson

National Heart, Lung, and Blood Institute (5T32HL007936-01A1)

  • Erick B Rios-Pérez
  • Jennifer J Knickelbine

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

Reviewing Editor

  1. Richard Aldrich, The University of Texas at Austin, United States

Version history

  1. Received: October 11, 2019
  2. Accepted: October 23, 2019
  3. Accepted Manuscript published: October 31, 2019 (version 1)
  4. Version of Record published: November 20, 2019 (version 2)

Copyright

© 2019, Eichel 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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  1. Catherine A Eichel
  2. Erick B Rios-Pérez
  3. Fang Liu
  4. Margaret B Jameson
  5. David K Jones
  6. Jennifer J Knickelbine
  7. Gail A Robertson
(2019)
A microtranslatome coordinately regulates sodium and potassium currents in the human heart
eLife 8:e52654.
https://doi.org/10.7554/eLife.52654

Share this article

https://doi.org/10.7554/eLife.52654

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