circHIPK3 prevents cardiac senescence by acting as a scaffold to recruit ubiquitin ligase to degrade HuR
Fengzhi Ding, Lin Lu, Chengjie Wu, Xiangbin Pan, Bin Liu, Yu Zhang, Yanli Wang, Weiliang Wu, Bing Yan, Yuqing Zhang, Xi‐Yong Yu, Yangxin Li
Abstract
We successfully generated CM-specific CKO mice for aging research. Our results showed that deletion of circHIPK3 led to exaggerated CM senescence and decreased cardiac function. As a scaffold, circHIPK3 enhanced the binding of E3 ubiquitin ligase β-TrCP and HuR in the cytoplasm, leading to the ubiquitination and degradation of HuR and reduced p21 activity. In addition, UMSC-Exos exerted an anti-senescence and cardio-protective effect by delivering circHIPK3. These findings pave the way to the development of new therapies for aging associated cardiac dysfunction.
Topics & Concepts
TelomereSenescenceUbiquitin ligaseUbiquitinBiologyCell biologyGene silencingWestern blotImmunoprecipitationSmall hairpin RNAMolecular biologyCancer researchRNACell cultureBiochemistryGeneticsDNAGeneCircular RNAs in diseasesRNA Research and SplicingMicroRNA in disease regulation