Fish species-specific TRIM gene FTRCA1 negatively regulates interferon response through attenuating IRF7 transcription
Fish species-specific TRIM gene FTRCA1 negatively regulates interferon response through attenuating IRF7 transcription
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鱼类特异性 TRIM 基因 FTRCA1 通过减弱 IRF7 转录负向调节干扰素反应
DOI：
10.1016/j.fsi.2019.04.297
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发表时间：
2019
影响因子：
4.7
通讯作者：
Zhang Yi Bing
中科院分区：
文献类型：
--
作者：
Wu Min;Dan Cheng;Gui Jian Fang;Zhang Yi Bing
在哺乳动物和鱼类中，新的证据强调TRIM家族成员在干扰素(干扰素)抗病毒免疫反应中发挥重要作用。FISH TRIM家族经历了前所未有的扩张，导致了FINTRIM亚家族的产生，它是鱼类特有的。我们最近的研究结果表明，FTRCA1(finTRIMC.Auratus1)可能是鲫鱼CarpC中鱼类特有的finTRIM成员。Auratusand作为负调制子，通过自噬-溶酶体降解蛋白激酶TBK1来下调鱼类干扰素的反应。在本研究中，我们发现FTRCA1也能抑制IRF7而不是IRF3对鲫鱼干扰素启动子的激活。从机制上讲，FTRCA1减弱IRF7转录水平，可能是由于IRF7 mRNA的加速衰退，导致IRF7蛋白水平降低，从而降低鱼类干扰素的表达。由于连接酶失活突变体和FTRCA1环缺失突变体失去了阻断IRF7激活鲫鱼干扰素启动子的能力，FTRCA1需要E3连接酶活性才能负性调节IRF7介导的干扰素应答。这些结果表明，FTRCA1是一个多方面的调节剂，针对不同的信号因子来塑造鱼对鲫鱼干扰素的反应。
In mammals and fish, emerging evidence highlights that TRIM family members play important roles in the interferon (IFN) antiviral immune response. Fish TRIM family has undergone an unprecedented expansion leading to generation of finTRIM subfamily, which is exclusively specific to fish. Our recent results have shown that FTRCA1 (finTRIMC. auratus1) is likely a fish species-specific finTRIM member in crucian carpC. auratusand acts as a negative modulator to downregulate fish IFN response by autophage-lysosomal degradation of protein kinase TBK1. In the present study, we found that FTRCA1 also impedes the activation of crucian carp IFN promoter by IRF7 but not by IRF3. Mechanistically, FTRCA1 attenuates IRF7 transcription levels likely due to enhanced decay of IRF7 mRNA, leading to reduced IRF7 protein levels and subsequently reduced fish IFN expression. E3 ligase activity is required for FTRCA1 to negatively regulate IRF7-mediated IFN response, because ligase-inactive mutants and the RING-deleted mutant of FTRCA1 lose the ability to block the activation of crucian carp IFN promoter by IRF7. These results together indicate that FTRCA1 is a multifaceted modulator to target different signaling factors for shaping fish IFN response in crucian carp.