Long noncoding RNA AANCR modulates innate antiviral responses by blocking miR-210-dependent MITA downregulation in teleo
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ng noncoding RNA AANCR modulates innate antiviral responses by blocking miR-210-dependent MITA downregulation in teleost fish, Miichthys miiuy 1,2
Qing Chu , Tianjun Xu
1,2,3,4*
1,2
1
, Weiwei Zheng , Renjie Chang & Lei Zhang
1
1
Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai 201306, China; 2 Laboratory of Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, 3
Qingdao 266237, China; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, 4
Shanghai 201306, China; National Pathogen Collection Center for Aquatic Animals, Shanghai Ocean University, Shanghai 201306, China Received May 22, 2020; accepted August 3, 2020; published online September 24, 2020
Viral infection induces the initiation of antiviral effectors and cytokines which are critical mediators of innate antiviral responses. The critical molecular determinants are responsible for triggering an appropriate immune response. Long noncoding RNAs (lncRNAs) have emerged as new gene modulators involved in various biological processes, while how lncRNAs operate in lower vertebrates are still unknown. Here, we discover a long noncoding RNA, termed antiviral-associated long noncoding RNA (AANCR), as a novel regulator for innate antiviral responses in teleost fish. The results indicate that fish MITA plays an essential role in host antiviral responses and inhibition of Siniperca chuatsi rhabdovirus (SCRV) production. miR-210 reduces MITA expression and suppress MITA-mediated antiviral responses, which may help viruses evade host antiviral responses. Further, AANCR functions as a competing endogenous RNA (ceRNA) for miR-210 to control protein abundance of MITA, thereby inhibiting SCRV replication and promoting antiviral responses. Our data not only shed new light on understanding the function role of lncRNA in biological processes in teleost fish, but confirmed the hypothesis that ceRNA networks exist widely in vertebrates. long noncoding RNAs, microRNA, ceRNA, MITA, antiviral responses, teleost fish Citation:
Chu, Q., Xu, T., Zheng, W., Chang, R., and Zhang, L. (2020). Long noncoding RNA AANCR modulates innate antiviral responses by blocking miR210-dependent MITA downregulation in teleost fish, Miichthys miiuy. Sci China Life Sci 63, https://doi.org/10.1007/s11427-020-1789-5
INTRODUCTION The innate antiviral responses are critical for efficient host defense against viral infection. In host cells, pattern recognition receptors (PRRs) detect the pathogen-associated molecular patterns (PAMPs) generated by invading viral pathogens to initiate antiviral responses. Among these PRRs, endosomal TLR3 and RIG-I-like receptors (RLRs)
play important roles in recognizing viral RNAs (Yoneyama and Fujita, 2009). Upon infection, TLR3 senses viral double-stranded RNA (dsRNA) in the endosome of certain immune cells, whereas RLRs recognize viral RNAs in the cytoplasm (Akira et al., 2006). After
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