生物
先天免疫系统
基因敲除
RNA干扰
细胞生物学
免疫系统
长非编码RNA
核糖核酸
基因
下调和上调
转录因子
抄写(语言学)
病毒学
遗传学
语言学
哲学
作者
Xiaoyun Jia,Meiqi Zhang,Haojia Wang,Cuiqin Cheng,Qiqi Li,Yiying Li,Ling-Dong Kong,Xihong Lan,Yuxi Wang,Liang Xue,Shaochun Yuan,Yao Wang,Anlong Xu
摘要
Abstract Increasing evidence suggests that natural antisense transcriptional lncRNAs regulate their adjacent coding genes to mediate diverse aspects of biology. Bioinformatics analysis of the previously identified antiviral gene ZNFX1 revealed neighboring lncRNA ZFAS1 transcribed on the opposite strand from ZNFX1 . Whether ZFAS1 exerts antiviral function via regulating the dsRNA sensor ZNFX1 is unknown. Here we found that ZFAS1 was upregulated by RNA and DNA viruses and type I IFNs (IFN‐I) dependent on Jak‐STAT signaling, similar to the transcription regulation of ZNFX1 . Knockdown of endogenous ZFAS1 partially facilitated viral infection, while ZFAS1 overexpression showed opposite effects. In addition, mice were more resistant to VSV infection with the delivery of human ZFAS1 . We further observed that ZFAS1 knockdown significantly inhibited IFNB1 expression and IFR3 dimerization, whereas ZFAS1 overexpression positively regulated antiviral innate immune pathways. Mechanistically, ZFAS1 positively regulated ZNFX1 expression and antiviral function by enhancing the protein stability of ZNFX1, thereby establishing a positive feedback loop to enhance antiviral immune activation status. In short, ZFAS1 is a positive regulator of antiviral innate immune response via regulating its neighbor gene ZNFX1, adding new mechanistic insight into lncRNA‐mediated regulation of signaling in innate immunity.
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