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

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 and channels ( and , respectively)...

Full description

Saved in:

Bibliographic Details
Published in:	eLife Vol. 8
Main Authors:	Eichel, Catherine A, Ríos-Pérez, Erick B, Liu, Fang, Jameson, Margaret B, Jones, David K, Knickelbine, Jennifer J, Robertson, Gail A
Format:	Journal Article
Language:	English
Published:	England eLife Science Publications, Ltd 31-10-2019 eLife Sciences Publications Ltd eLife Sciences Publications, Ltd
Subjects:	action potential Arrhythmia Associations Biochemistry Cardiac arrhythmia Cardiology Cardiomyocytes Cell Biology co-knockdown cotranslation Death ERG1 Potassium Channel - genetics ERG1 Potassium Channel - metabolism Fluorescence Gene Expression Regulation Heart Heart - physiology HEK293 Cells Humans Immunoglobulins ion channels KCNH2 Localization Messenger RNA NAV1.5 Voltage-Gated Sodium Channel - genetics NAV1.5 Voltage-Gated Sodium Channel - metabolism Potassium - metabolism Potassium currents Protein Biosynthesis Proteins RNA RNA, Messenger - metabolism SCN5A Sodium Sodium - metabolism Sodium currents Structural Biology and Molecular Biophysics Sudden cardiac death Transfection United States > US KCNH2 co-knockdown cell biology cotranslation structural biology SCN5A molecular biophysics action potential human ion channels
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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 and channels ( and , respectively) are associated in defined complexes during protein translation. Using biochemical, electrophysiological and single-molecule fluorescence localization approaches, we find that roughly half the translational complexes contain 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Department of Pharmacology, University of Michigan Medical School, Ann Arbor, United States.
ISSN:	2050-084X 2050-084X
DOI:	10.7554/eLife.52654