Li Haimin, Du Liuyang, Li Juan, Huang Yanming, Lu Chenhe, Deng Tingjuan, Yan Yan, Jin Yulan, Wu Wei, Gu Jinyan, Zhou Jiyong
MOA Key Laboratory of Animal Virology, Zhejiang University Center for Veterinary Sciences, Hangzhou, China.
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University, Hangzhou, China.
PLoS Pathog. 2024 Dec 17;20(12):e1012712. doi: 10.1371/journal.ppat.1012712. eCollection 2024 Dec.
Circular RNAs (circRNAs) exert diverse biological functions in different processes. However, the role of circRNAs during virus infection is mostly unknown. Herein, we explored the characteristics of host circRNAs using alphaherpesvirus pseudorabies virus (PRV) as a model. PRV infection upregulated the expression of circRNA circ29164, which does not encode a protein. RNA pulldown assays identified that circ29164 interacts with the microRNA ssc-miRNA-24-3p. Further analysis indicated that ssc-miR-24-3p targets the mRNA encoding kelch-like ECH-associated protein 1 (KEAP1), and circ29164 competitively binds to ssc-miR-24-3p to prevent it binding to Keap1. Apoptosis detection demonstrated that circ29164 or Keap1 overexpression, but not knockdown, induced caspase 3 activity and the release of cytochrome C from mitochondria, and inhibited PRV replication. Taken together, these data identified a previously undiscovered circRNA, circ29164, which inhibits PRV replication by competitively binding to ssc-24-3p to maintain KEAP1 levels.
环状RNA（circRNAs）在不同过程中发挥多种生物学功能。然而，circRNAs在病毒感染过程中的作用大多未知。在此，我们以甲型疱疹病毒伪狂犬病病毒（PRV）为模型，探索宿主circRNAs的特征。PRV感染上调了不编码蛋白质的circRNA circ29164的表达。RNA下拉试验确定circ29164与微小RNA ssc - miRNA - 24 - 3p相互作用。进一步分析表明，ssc - miR - 24 - 3p靶向编码kelch样ECH相关蛋白1（KEAP1）的mRNA，且circ29164竞争性结合ssc - miR - 24 - 3p以阻止其与Keap1结合。细胞凋亡检测表明，circ29164或Keap1的过表达而非敲低，诱导了半胱天冬酶3活性以及细胞色素C从线粒体的释放，并抑制了PRV复制。综上所述，这些数据鉴定出一种先前未被发现的circRNA，即circ29164，它通过竞争性结合ssc - 24 - 3p以维持KEAP1水平来抑制PRV复制。
