1. Negative feedback of SNRK to circ-SNRK regulates cardiac function post-myocardial infarction
- Author
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Xiao-Xiao Liu, Zhi-Yan Wang, and Yun-Fei Deng
- Subjects
Cardiac function curve ,Myocardial Infarction ,Regulator ,Protein Serine-Threonine Kinases ,Feedback ,Negative feedback ,Neuro-Oncological Ventral Antigen ,medicine ,Animals ,Myocytes, Cardiac ,Myocardial infarction ,Molecular Biology ,Heart Failure ,ATP synthase ,biology ,Kinase ,Chemistry ,Alternative splicing ,RNA-Binding Proteins ,RNA, Circular ,Cell Biology ,medicine.disease ,Rats ,Cell biology ,MicroRNAs ,Heart failure ,biology.protein - Abstract
A limited delivery of oxygen and metabolic substrate to the heart caused by myocardial infarction (MI) impairs the cardiac function, and often results in heart failure. Here, we identified a circRNA (circ-SNRK) from SNRK (sucrose nonfermenting 1-related kinase, which can increase the cardiac mitochondrial efficiency) in cardiomyocytes (CMs). Circ-SNRK can sponge the miR-33 and in turn improved the ATP synthesis via SNRK, proving the existence of circ-SNRK - miR-33 - SNRK axis. Furthermore, we found that protein NOVA1 (NOVA alternative splicing regulator 1) could accelerate the circ-SNRK formation; a cleaved peptide (~55 kDa) from SNRK enters the nucleus and blocks the cyclization of circ-SNRK via binding to NOVA1. The aforementioned negative feedback of SNRK to circ-SNRK limited the SNRK at a proper level, and inhibited the protective role of circ-SNRK in ischemic heart. In addition, our in vivo experiment indicated that the overexpression of exogenic circ-SNRK could break this loop and improves the cardiac function post-MI in rats. Together, our results demonstrated that the negative loop of circ-SNRK with SNRK regulates the energy metabolism in CMs, thus might be a potential therapeutic target for heart failure.
- Published
- 2021
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