Mir-24 regulates junctophilin-2 expression in cardiomyocytes.
BACKGROUND
Failing cardiomyocytes exhibit decreased efficiency of excitation-contraction (E-C) coupling. The downregulation of junctophilin-2 (JP2), a protein anchoring the sarcoplasmic reticulum to T-tubules, 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.


RESULTS
Bioinformatic analysis predicted 2 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 upregulated in failing cardiomyocytes. Adenovirus-directed overexpression of miR-24 in cardiomyocytes decreased JP2 expression and reduced Ca(2+) 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.
State Key Laboratory of Biomembrane and Membrane Biotechnology, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Third Hospital, College of Engineering and College of Life Sciences, Peking University, China.
Ming
M
Xu
Hao-Di
HD
Wu
Rong-Chang
RC
Li
Hai-Bo
HB
Zhang
Meng
M
Wang
Jin
J
Tao
Xin-Heng
XH
Feng
Yun-Bo
YB
Guo
Su-Fang
SF
Li
Shao-Ting
ST
Lai
Peng
P
Zhou
Lin-Lin
LL
Li
Hua-Qian
HQ
Yang
Guan-Zheng
GZ
Luo
Yan
Y
Bai
Jianzhong J
JJ
Xi
Wei
W
Gao
Qi-De
QD
Han
You-Yi
YY
Zhang
Xiu-Jie
XJ
Wang
Xu
X
Meng
Shi-Qiang
SQ
Wang
D000818:Animals; D001024:Aortic Valve Stenosis / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D019295:Computational Biology; D056966:Excitation Contraction Coupling / Q000502:physiology; D006333:Heart Failure / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D023421:Models, Animal; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000502:physiology; D015854:Up-Regulation
C574736:MIRN24 microRNA, rat; D008565:Membrane Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; C412507:junctophilin; D002118:Calcium