斑马鱼TBK1的两个剪接异构体负调控Ⅰ型干扰素信号通路
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- 英文论文题名：Two novel splicing variants of zebrafish TBK1 function as negative regulators of the type Ⅰ IFNs signaling pathway
- 论文作者：胡祎玮 ; 武小曼 ; 任诗思 ; 聂品 ; 昌鸣先
- 英文论文作者：HU Yiwei ; WU Xiaoman ; REN Shisi ; NIE Pin ; CHANG Mingxian ; State Key Laboratory of Freshwater Ecology and Biotechnology ; Institute of Hydrobiology ; Chinese Academy of Sciences
- 年：2016
- 作者机构：中国科学院水生生物研究所淡水生态与生物技术国家重点实验室;
- 论文关键词：斑马鱼 ; Ⅰ型干扰素 ; TBK1 ; 剪接异构体 ; 转录调控
- 英文论文关键词：Zebrafish ; Type Ⅰ IFN ; TBK1 ; Splicing variants ; transcript regulation
- 会议召开时间：2016-11-02
- 会议录名称：2016年中国水产学会学术年会论文摘要集
- 语种：中文
- 分类号：S917.4
- 学会代码：OGSB
- 会议名称：2016年中国水产学会学术年会
- 会议地点：中国四川成都
- 主办单位：中国水产学会、四川省水产学会
- 学会名称：中国水产学会
- 页数：1
- 文件大小：507k
- 原文格式：D
- 会议级别：全国
摘要
TBK1对天然免疫中IRF3的磷酸化起到重要的调控作用,从而影响Ⅰ型干扰素的表达。在此研究中,我们克隆得到斑马鱼TBK1基因的两个剪接异构体,将其命名为TBK1-tv1,TBK1-tv2。与TBK1相比,TBK1-tv1缺失第3-4个外显子,而TBK1-tv2缺失了第4-18个外显子。这两个异构体不能像TBK1那样显著抑制SVCV的增殖;同时,SVCV病毒的感染不能诱导它们的表达。过表达TBK1的剪接异构体能显著下调RIG-I、MAVS、TBK1以及IRF3诱导的Ⅰ型干扰素启动子的活性。荧光定量结果表明,TBK1的剪接异构体能显著抑制MAVS以及TBK1诱导的干扰素以及干扰素诱导相关基因的表达。这些研究结果揭示了TBK1的剪接异构体在Ⅰ型干扰素信号通路中起着负调控的作用。
TBK1 has a pivotal role in regulating the phosphorylating of IRF3 in the innate immune response, thus influences the expression of type I IFNs. In this study, we identified two TBK1 variants from zebrafish and named them as TBK1_tv1 and TBK1_tv2. Compared with TBK1, TBK1_tv1 lacks exons 3-4, while TBK1_tv2 lacks exons 4-18. We found that SVCV infection can not induce the expression of TBK1 variants, and that TBK1 variants have no role for viral replication. Furthermore, overexpression of TBK1_tv1 and TBK1_tv2 can significantly inhibit the activity of IFN1 or IFN3 promoters, which is induced by RIG-I, MAVS, TBK1 and TRF3. Realtime PCR indicated that overexpression of TBK1_tv1 and TBK1_tv2 significantly decreased the production of IFN1 and IFN-stimulated genes induced by MAVS and TBK1. These data provide evidence that TBK1 variants act as negative regulators in the type Ⅰ IFN signaling pathway.
TBK1 has a pivotal role in regulating the phosphorylating of IRF3 in the innate immune response, thus influences the expression of type I IFNs. In this study, we identified two TBK1 variants from zebrafish and named them as TBK1_tv1 and TBK1_tv2. Compared with TBK1, TBK1_tv1 lacks exons 3-4, while TBK1_tv2 lacks exons 4-18. We found that SVCV infection can not induce the expression of TBK1 variants, and that TBK1 variants have no role for viral replication. Furthermore, overexpression of TBK1_tv1 and TBK1_tv2 can significantly inhibit the activity of IFN1 or IFN3 promoters, which is induced by RIG-I, MAVS, TBK1 and TRF3. Realtime PCR indicated that overexpression of TBK1_tv1 and TBK1_tv2 significantly decreased the production of IFN1 and IFN-stimulated genes induced by MAVS and TBK1. These data provide evidence that TBK1 variants act as negative regulators in the type Ⅰ IFN signaling pathway.
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