Liu Guiliang, Xin Shiying, Geng Shang, Zheng Weiwei, Xu Tianjun, Sun Yuena
Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, China.
Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, China; Laboratory of Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China.
Fish Shellfish Immunol. 2023 May;136:108697. doi: 10.1016/j.fsi.2023.108697. Epub 2023 Mar 23.
Fusion gene is a new gene formed by the fusion of all or part of the sequences of two genes, it is caused by chromosome translocation, middle deletion or chromosome inversion. Numerous studies in the past have continuously shown that gene fusions are tightly associated with the occurrence and development of various diseases, especially cancer. Many fusion genes have been identified in humans. However, few fusion genes have been identified in fish. In this study, a novel NLRC3-NLRP12 fusion gene was identified in the Miichthys miiuy (miiuy croaker) by quantitative real-time PCR (qRT-PCR), PCR, and Sanger sequencing. This fusion gene is fused by two genes related to NLRs (nucleotide binding domain and oligomerization domain like receptors). We found that the expression of the NLRC3-NLRP12 fusion gene was significantly upregulated after infection with Vibrio anguillarum (V. anguillarum) or stimulation with lipopolysaccharide (LPS). In addition, the NLRC3-NLRP12 fusion gene was strongly induced by V. anguillarum infection, peaking within the kidney and liver at 12 h post infection. Further functional experiments showed that overexpression of NLRC3-NLRP12 significantly inhibited nuclear factor kappa-B (NF-κB) activation. This study suggests that the newly discovered NLRC3-NLRP12 fusion genes may play an important role in innate immunity in miiuy croaker.
融合基因是由两个基因的全部或部分序列融合形成的新基因，它是由染色体易位、中间缺失或染色体倒位引起的。过去的大量研究不断表明，基因融合与各种疾病尤其是癌症的发生和发展密切相关。在人类中已经鉴定出许多融合基因。然而，在鱼类中鉴定出的融合基因很少。在本研究中，通过定量实时PCR（qRT-PCR）、PCR和桑格测序，在鮸鱼中鉴定出一种新的NLRC3-NLRP12融合基因。该融合基因由两个与NLRs（核苷酸结合域和寡聚化结构域样受体）相关的基因融合而成。我们发现，在用鳗弧菌感染或用脂多糖（LPS）刺激后，NLRC3-NLRP12融合基因的表达显著上调。此外，鳗弧菌感染强烈诱导NLRC3-NLRP12融合基因，在感染后12小时在肾脏和肝脏中达到峰值。进一步的功能实验表明，NLRC3-NLRP12的过表达显著抑制核因子κB（NF-κB）的激活。本研究表明，新发现的NLRC3-NLRP12融合基因可能在鮸鱼的先天免疫中发挥重要作用。
