Negative feedback of SNRK to circ-SNRK regulates cardiac function post-myocardial infarction

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 mitocho...

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Vydané v:Cell death and differentiation Ročník 29; číslo 4; s. 709 - 721
Hlavní autori: Wang, Zhi-Yan, Liu, Xiao-Xiao, Deng, Yun-Fei
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: England Nature Publishing Group 01.04.2022
Predmet:
Alternative splicing
Animals
Cardiac function
Cardiomyocytes
Congestive heart failure
Energy metabolism
Feedback
Heart attacks
Heart failure
Heart Failure - metabolism
Ischemia
Kinases
MicroRNAs - genetics
Mitochondria
Myocardial infarction
Myocardial Infarction - genetics
Myocardial Infarction - metabolism
Myocytes, Cardiac - metabolism
Neuro-Oncological Ventral Antigen
Protein Serine-Threonine Kinases - genetics
Rats
RNA, Circular - genetics
RNA-Binding Proteins - metabolism
Sucrose
Therapeutic targets
ISSN:1350-9047, 1476-5403, 1476-5403
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Shrnutí: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.
Bibliografia:ObjectType-Article-1
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ISSN:1350-9047
1476-5403
1476-5403
DOI:10.1038/s41418-021-00885-x