A previously unidentified circRNA inhibits virus replication by regulating the miR-24-3p/KEAP1 axis.

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 t...

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Main Authors: Haimin Li, Liuyang Du, Juan Li, Yanming Huang, Chenhe Lu, Tingjuan Deng, Yan Yan, Yulan Jin, Wei Wu, Jinyan Gu, Jiyong Zhou
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2024-12-01
Series:PLoS Pathogens
Online Access:https://doi.org/10.1371/journal.ppat.1012712
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author Haimin Li
Liuyang Du
Juan Li
Yanming Huang
Chenhe Lu
Tingjuan Deng
Yan Yan
Yulan Jin
Wei Wu
Jinyan Gu
Jiyong Zhou
author_facet Haimin Li
Liuyang Du
Juan Li
Yanming Huang
Chenhe Lu
Tingjuan Deng
Yan Yan
Yulan Jin
Wei Wu
Jinyan Gu
Jiyong Zhou
author_sort Haimin Li
collection DOAJ
description 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.
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spelling doaj-art-5c0ceee2f6b94556a4292c52d535995d2025-08-20T02:59:45ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742024-12-012012e101271210.1371/journal.ppat.1012712A previously unidentified circRNA inhibits virus replication by regulating the miR-24-3p/KEAP1 axis.Haimin LiLiuyang DuJuan LiYanming HuangChenhe LuTingjuan DengYan YanYulan JinWei WuJinyan GuJiyong ZhouCircular 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.https://doi.org/10.1371/journal.ppat.1012712
spellingShingle Haimin Li
Liuyang Du
Juan Li
Yanming Huang
Chenhe Lu
Tingjuan Deng
Yan Yan
Yulan Jin
Wei Wu
Jinyan Gu
Jiyong Zhou
A previously unidentified circRNA inhibits virus replication by regulating the miR-24-3p/KEAP1 axis.
PLoS Pathogens
title A previously unidentified circRNA inhibits virus replication by regulating the miR-24-3p/KEAP1 axis.
title_full A previously unidentified circRNA inhibits virus replication by regulating the miR-24-3p/KEAP1 axis.
title_fullStr A previously unidentified circRNA inhibits virus replication by regulating the miR-24-3p/KEAP1 axis.
title_full_unstemmed A previously unidentified circRNA inhibits virus replication by regulating the miR-24-3p/KEAP1 axis.
title_short A previously unidentified circRNA inhibits virus replication by regulating the miR-24-3p/KEAP1 axis.
title_sort previously unidentified circrna inhibits virus replication by regulating the mir 24 3p keap1 axis
url https://doi.org/10.1371/journal.ppat.1012712
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