Letter abstract
Nature Medicine 13, 486 - 491 (2007)
Published online: 1 April 2007 | doi:10.1038/nm1569
The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2
Baofeng Yang1,2,5, Huixian Lin2,3,4,5, Jiening Xiao2,3,4,5, Yanjie Lu1,2, Xiaobin Luo2,3,4, Baoxin Li1, Ying Zhang1, Chaoqian Xu1, Yunlong Bai1, Huizhen Wang1,3, Guohao Chen1 & Zhiguo Wang2,3,4
MicroRNAs (miRNAs) are endogenous noncoding RNAs, about 22 nucleotides in length, that mediate post-transcriptional gene silencing by annealing to inexactly complementary sequences in the 3'-untranslated regions of target mRNAs1, 2, 3. Our current understanding of the functions of miRNAs relies mainly on their tissue-specific or developmental stage-dependent expression and their evolutionary conservation, and therefore is primarily limited to their involvement in developmental regulation and oncogenesis2. Of more than 300 miRNAs that have been identified, miR-1 and miR-133 are considered to be muscle specific4, 5, 6. Here we show that miR-1 is overexpressed in individuals with coronary artery disease, and that when overexpressed in normal or infarcted rat hearts, it exacerbates arrhythmogenesis. Elimination of miR-1 by an antisense inhibitor in infarcted rat hearts relieved arrhythmogenesis. miR-1 overexpression slowed conduction and depolarized the cytoplasmic membrane by post-transcriptionally repressing KCNJ2 (which encodes the K+ channel subunit Kir2.1) and GJA1 (which encodes connexin 43), and this likely accounts at least in part for its arrhythmogenic potential. Thus, miR-1 may have important pathophysiological functions in the heart, and is a potential antiarrhythmic target.
- Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang 150086, China.
- Institute of Cardiovascular Research, Harbin Medical University, Harbin, Heilongjiang 150086, China.
- Research Center, Montreal Heart Institute, 5000 Belanger East, Montreal PQ H1T 1C8, Canada.
- Department of Medicine, University of Montreal, Montreal PQ H3C 3J7, Canada.
- These authors contributed equally to this work.
Correspondence to: Zhiguo Wang2,3,4 e-mail: wz.email@gmail.com
Correspondence to: Baofeng Yang1,2,5 e-mail: yangbf@ems.hrbmu.edu.cn
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