A Novel Intronic Circular RNA Antagonizes Influenza Virus by Absorbing a microRNA That Degrades CREBBP and Accelerating IFN-β Production
Zhiyuan Qu, Fei Meng, Jianzhong Shi, Guohua Deng, Xianying Zeng, Jinying Ge, Yanbing Li, Liling Liu, Pucheng Chen, Yongping Jiang, Chengjun Li, Hualan Chen
Abstract
Circular RNAs (circRNAs) are new members of the long noncoding RNA families and have been identified in a variety of organisms, including plants, animals, and humans. Accumulating data indicate that circRNAs perform multiple functions in a variety of cellular processes associated with human diseases, such as Alzheimer's disease and cancer; however, the roles of circRNAs in virus infection have been largely uninvestigated. In this study, we investigated the cellular circRNA response upon influenza virus infection and found that 411 circRNAs were differentially expressed in the virus-infected cells. We identified a novel human intronic circRNA (we named AIVR) that antagonizes influenza virus replication. Upregulated circRNA AIVR absorbs an miRNA that binds the mRNA of CREBBP, leading to an increase in the cellular expression of CREBBP and then accelerating IFN-β production. This study advances the understanding of the roles of circRNAs in the cellular innate antiviral response.