Cold-Inducible RNA-Binding Protein Regulates Cardiac Repolarization by Targeting Transient Outward Potassium Channels. Issue 10 (8th May 2015)

• Record Type: Journal Article
• Authors: Li, Jun; Xie, Duanyang; Huang, Jian; Lv, Fei; Shi, Dan; Liu, Yi; Lin, Li; Geng, Li; Wu, Yufei; Liang, Dandan; Chen, Yi-Han
• Is Part Of: Circulation research. Volume 116:Issue 10(2015)
• Publication Date: 2015-05-08
• Subjects: Cardiovascular system -- Periodicals; Blood -- Circulation -- Periodicals; Blood Circulation; Cardiovascular System; Vascular Diseases; Sang -- Circulation -- Périodiques; Appareil cardiovasculaire -- Périodiques; 612.1
• DOI: 10.1161/CIRCRESAHA.116.306287
• Languages: English
• ISSNs: 0009-7330

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title> <underline>Rationale:</underline> </title> <p>Cold-inducible RNA-binding protein (CIRP) is constitutively expressed at low levels across various tissues. It is rapidly upregulated by multiple stresses, underlying a general role for CIRP in organic adaptations to pathophysiological conditions. However, the role of CIRP in the heart remains unclear.</p> </sec> <sec> <title> <underline>Objective:</underline> </title> <p>To examine the biofunctions of CIRP in the mammalian heart.</p> </sec> <sec> <title> <underline>Methods and Results:</underline> </title> <p>Rats with targeted disruption of <italic>Cirp</italic> were generated using the TALEN (transcription activator-like effector nucleases)-based genome editing technique. The <italic>Cirp</italic>-knockout rats had structurally and functionally normal hearts. Resting ECG recordings revealed a short rate-corrected QT (QTc) interval in <italic>Cirp</italic>-null rats without any abnormalities in PR interval, RR interval or QRS waves as compared to wild-type animals. The shortened QTc interval from <italic>Cirp</italic> ablation was tightly linked to an abbreviated action potential duration in cardiac myocytes, which was attributable to increased transient outward potassium current (<italic>I</italic><sub>to</sub>). Furthermore, our findings uncovered that CIRP protein selectively bonded to <italic>KCND2</italic> and <italic>KCND3</italic> mRNAs encoding the functional α-subunits of <italic>I</italic><sub>to</sub> channel proteins. CIRP deficiency did not change the transcriptional activity of <italic>KCND2</italic> or <italic>KCND3</italic>, but it facilitated their translation. <italic>Cirp</italic> knockout had no effect on the functional expression of ion channels other than <italic>I</italic><sub>to</sub> channels.</p> </sec> <sec> <title> <underline>Conclusions:</underline> </title> <p>CIRP modulates cardiac repolarization by negatively adjusting the expression and function of <italic>I</italic><sub>to</sub> channels. Our study may open a window to decipher the potential function of RNA-binding proteins in bioelectric activity.</p> </sec> </abstract>