Long non-coding RNA CCRR controls cardiac conduction via regulating intercellular coupling. Issue 1 (December 2018)

• Record Type: Journal Article
• Authors: Zhang, Yong; Sun, Lihua; Xuan, Lina; Pan, Zhenwei; Hu, Xueling; Liu, Hongyu; Bai, Yunlong; Jiao, Lei; Li, Zhange; Cui, Lina; Wang, Xiaoxue; Wang, Siqi; Yu, Tingting; Feng, Bingbing; Guo, Ying; Liu, Zonghong; Meng, Weixin; Ren, Hequn; Zhu, Jiyuan; Zhao, Xuyun; Yang, Chao; Zhang, Ying; Xu, Chaoqian; Wang, Zhiguo; Lu, Yanjie; Shan, Hongli; Yang, Baofeng
• Is Part Of: Nature communications. Volume 9:Issue 1(2018)
• Page Start: 1
• Page End: 14
• Publication Date: 2018-12
• Subjects: Biology -- Periodicals; Physical sciences -- Periodicals; 505
• DOI: 10.1038/s41467-018-06637-9
• Languages: English
• ISSNs: 2041-1723

Abstract

Abstract Long non-coding RNAs (lncRNAs) have emerged as a new class of gene expression regulators playing key roles in many biological and pathophysiological processes. Here, we identify cardiac conduction regulatory RNA (CCRR) as an antiarrhythmic lncRNA. CCRR is downregulated in a mouse model of heart failure (HF) and in patients with HF, and this downregulation slows cardiac conduction and enhances arrhythmogenicity. Moreover, CCRR silencing induces arrhythmias in healthy mice. CCRR overexpression eliminates these detrimental alterations. HF or CCRR knockdown causes destruction of intercalated discs and gap junctions to slow longitudinal cardiac conduction. CCRR overexpression improves cardiac conduction by blocking endocytic trafficking of connexin43 (Cx43) to prevent its degradation via binding to Cx43-interacting protein CIP85, whereas CCRR silence does the opposite. We identified the functional domain of CCRR, which can reproduce the functional roles and pertinent molecular events of full-length CCRR. Our study suggests CCRR replacement a potential therapeutic approach for pathological arrhythmias. Long noncoding RNAs have been shown to play a role in cardiovascular disease. Here, the authors identify a lncRNA named CCRR, whose downregulation in failing hearts causes cardiac conduction disturbances by altering the endocytic trafficking of Cx43.