A Previously Undiscovered Circular RNA, circTNFAIP3, and Its Role in Coronavirus Replication

被引:13
作者
Du, Liuyang [1 ,2 ]
Wang, Xingbo [2 ]
Liu, Junli [1 ]
Li, Jiarong [2 ]
Wang, Shengnan [2 ]
Lei, Jing [1 ]
Zhou, Jiyong [2 ,3 ,4 ]
Gu, Jinyan [2 ]
机构
[1] Nanjing Agr Univ, Coll Vet Med, Inst Immunol, Nanjing, Peoples R China
[2] Zhejiang Univ, MOA Key Lab Anim Virol, Ctr Vet Sci, Hangzhou, Peoples R China
[3] Zhejiang Univ, Collaborat Innovat Ctr, Affiliated Hosp 1, Hangzhou, Peoples R China
[4] Zhejiang Univ, State Key Lab Diag & Treatment Infect Dis, Affiliated Hosp 1, Hangzhou, Peoples R China
来源
MBIO | 2021年 / 12卷 / 06期
关键词
deltacoronavirus; circular RNA; circTNFAIP3; virus replication; apoptosis; NF-KAPPA-B; PORCINE DELTACORONAVIRUS; PROGNOSTIC MARKER; DIARRHEA; A20; APOPTOSIS; CANCER; SWINE; TRANSLATION; EXPRESSION;
D O I
10.1128/mBio.02984-21
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Circular RNAs (circRNAs) are a newly discovered class of noncoding RNAs (ncRNAs) present in various tissues and cells. However, the functions of most circRNAs have not been verified experimentally. Here, using deltacoronavirus as a model, differ-entially expressed circRNAs in cells with or without deltacoronavirus infection were ana-lyzed by RNA sequencing to characterize the cellular responses to RNA virus infection. More than 57,000 circRNA candidates were detected, and seven significantly dysregu-lated circRNAs were quantitated by real-time reverse transcription-PCR. We discovered a previously unidentified circRNA derived from the TNFAIP3 gene, named circTNFAIP3, which is distributed and expressed widely in various tissues. RNA viruses, including del-tacoronaviruses, rather than DNA viruses tend to activate the expression of endoge-nous circTNFAIP3. Overexpression of circTNFAIP3 promoted deltacoronavirus replication by reducing the apoptosis, while silencing of circTNFAIP3 inhibited deltacoronavirus replication by enhancing the apoptosis. In summary, our work provides useful circRNA-related information to facilitate investigation of the underlying mechanism of deltacoro-navirus infection and identifies a novel circTNFAIP3 that promotes deltacoronavirus rep-lication via regulating apoptosis. IMPORTANCE CircRNAs, a new class of ncRNAs, play important roles in cell growth, neural development, carcinogenesis, and anticarcinogenesis. Porcine deltacoronavirus is an emerging enteropathogenic coronavirus that causes diarrhea, but the role of host circRNAs in regulating its infection is unknown. Here, we performed expression profiling of circRNAs in mock-and deltacoronavirus-infected cells and identified the novel differentially expressed circular RNA circTNFAIP3. We demonstrate that circTNFAIP3 pro-motes deltacoronavirus replication by inhibiting apoptosis. Our findings first illustrate that circRNA can act as an apoptosis negative regulator during RNA virus infection and help to explore the underlying mechanism of deltacoronavirus infection.
引用
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页数:20
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