MicroRNA Biophysically Modulates Cardiac Action Potential by Direct Binding to Ion Channel - Sorbonne Université Access content directly
Journal Articles Circulation Year : 2021

MicroRNA Biophysically Modulates Cardiac Action Potential by Direct Binding to Ion Channel

Xiaoping Wan
  • Function : Author
Adrienne T Dennis
  • Function : Author
Emre Bektik
Xianyao Xu
  • Function : Author
Daniel H Gratz
  • Function : Author
Thomas J Hund
Peter J Mohler
Kenneth R Laurita
Ji-Dong Fu

Abstract

BACKGROUND: MicroRNAs (miRs) play critical roles in regulation of numerous biological events, including cardiac electrophysiology and arrhythmia, through a canonical RNA interference mechanism. It remains unknown whether endogenous miRs modulate physiologic homeostasis of the heart through noncanonical mechanisms. METHODS: We focused on the predominant miR of the heart (miR1) and investigated whether miR1 could physically bind with ion channels in cardiomyocytes by electrophoretic mobility shift assay, in situ proximity ligation assay, RNA pull down, and RNA immunoprecipitation assays. The functional modulations of cellular electrophysiology were evaluated by inside-out and whole-cell patch clamp. Mutagenesis of miR1 and the ion channel was used to understand the underlying mechanism. The effect on the heart ex vivo was demonstrated through investigating arrhythmia-associated human single nucleotide polymorphisms with miR1-deficient mice.

Dates and versions

hal-03947182 , version 1 (27-02-2023)

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Cite

Dandan Yang, Xiaoping Wan, Adrienne T Dennis, Emre Bektik, Zhihua Wang, et al.. MicroRNA Biophysically Modulates Cardiac Action Potential by Direct Binding to Ion Channel. Circulation, 2021, 143, pp.1597 - 1613. ⟨10.1161/circulationaha.120.050098⟩. ⟨hal-03947182⟩
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