Long noncoding RNA AVAN promotes antiviral innate immunity by interacting with TRIM25 and enhancing the transcription of FOXO3a.

Chengcai Lai, Lihui Liu, Qinghua Liu, Keyu Wang, Sijie Cheng, Lingna Zhao, Min Xia, Cheng Wang, Yueqiang Duan, Lili Zhang, Ziyang Liu, Jianjun Luo, Xiliang Wang, Runsheng Chen, Penghui Yang

Cell death and differentiation 2021 Oct

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Accumulating evidence has shown that long noncoding RNAs (lncRNAs) are involved in several biological processes, including immune responses. However, the role of lncRNAs in antiviral innate immune responses remains largely elusive. Here, we identify an uncharacterized human lncRNA AVAN from influenza A virus (IAV) infected patients, that is significantly upregulated following RNA virus infection. During IAV infection, AVAN play an indispensable role in antiviral immune responses. In vivo, we enforced the expression of AVAN in transgenic mice or adeno-associated virus encoding AVAN delivery system and found that AVAN significantly alleviated IAV virulence and virus replication. Mechanistically, nuclear AVAN positively regulates the transcription of forkhead box O3A (FOXO3a) by associating with its promoter and inducing chromatin remodeling to promote neutrophil chemotaxis. Meanwhile, cytoplasmic AVAN binds directly to the E3 ligase TRIM25 and enhances TRIM25-mediated K63-linked ubiquitination of RIG-I, thereby promoting TRIM25- and RIG-I-mediated antiviral innate immune responses, including the induction of type I interferon and ISGs. Moreover, AVAN binds to the B Box/CCD domain of TRIM25 and 1-200nt of AVAN were the functional moieties. Collectively, our findings highlight the potential clinical implications of human lncRNA AVAN as a key positive regulator of the antiviral innate immune response and a promising target for developing broad antiviral therapeutics. © 2021. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.

Citation

Chengcai Lai, Lihui Liu, Qinghua Liu, Keyu Wang, Sijie Cheng, Lingna Zhao, Min Xia, Cheng Wang, Yueqiang Duan, Lili Zhang, Ziyang Liu, Jianjun Luo, Xiliang Wang, Runsheng Chen, Penghui Yang. Long noncoding RNA AVAN promotes antiviral innate immunity by interacting with TRIM25 and enhancing the transcription of FOXO3a. Cell death and differentiation. 2021 Oct;28(10):2900-2915