A microtranslatome coordinately regulates sodium and potassium currents in the human heart
- 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
Margaret B Jameson
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.
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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A microtranslatome coordinately regulates sodium and potassium currents in the human heart
eLife 8:e52654.
https://doi.org/10.7554/eLife.52654
