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.
- Gail A Robertson
- 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.
- Richard Aldrich, The University of Texas at Austin, United States
- Received: October 11, 2019
- Accepted: October 23, 2019
- Accepted Manuscript published: October 31, 2019 (version 1)
© 2019, Eichel et al.
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