Mir-24 Regulates Junctophilin-2 Expression in Cardiomyocytes
Rationale: Failing cardiomyocytes exhibit decreased efficiency of excitation-contraction (E-C) coupling. The down-regulation of junctophilin-2 (JP2), a protein anchoring the sarcoplasmic reticulum (SR) to T-tubules (TTs), has been identified as a major mechanism underlying the defective E-C coupling. However, the regulatory mechanism of JP2 remains unknown.
Objective: To determine whether microRNAs regulate JP2 expression.
Methods and Results: Bioinformatic analysis predicted two potential binding sites of miR-24 in the 3’-untranslated regions of JP2 mRNA. Luciferase assays confirmed that miR-24 suppressed JP2 expression by binding to either of these sites. In the aortic stenosis model, miR-24 was up-regulated in failing cardiomyocytes. Adenovirus-directed over-expression of miR-24 in cardiomyocytes decreased JP2 expression and reduced Ca2+ transient amplitude and E-C coupling gain.
Conclusions: MiR-24-mediated suppression of JP2 expression provides a novel molecular mechanism for E-C coupling regulation in heart cells, and suggests a new target against heart failure.
- Received July 12, 2012.
- Accepted August 13, 2012.
- Copyright © 2012, American Heart Association