Mitochondria-localised ZNFX1 functions as a dsRNA sensor to initiate antiviral responses through MAVS

Wang, Yao; Yuan, Shaochun; Jia, Xiaoyun; Ge, Yong; Tao, Ling; Nie, Meng; Lan, Xihong; Chen, Shangwu; Xu, Anlong

doi:10.1038/s41556-019-0416-0

Cited by 91 publications

(95 citation statements)

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“…Zinc nger NFX1-type containing 1 (ZNFX1) encodes an interferon (IFN)-stimulated, mitochondriallocalized dsRNA sensor capable of restricting the replication of RNA viruses (39). While its antiviral functions may not be relevant to the progression of human tumors, its antisense lncRNA ZFAS1 (zinc nger antisense 1) is well known for promoting growth of melanoma and other tumors (40).…”

Section: Discussionmentioning

confidence: 99%

Analysis Of Candidate Genes Expected To Be Essential For Melanoma Surviving

Krivosheeva

Filatova

Moshkovskii

et al. 2020

Preprint

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Cancers may be treated by selective targeting of the genes vital for their survival. A number of attempts have led to discovery of several genes essential for surviving of tumor cells of different types. In this work, we tried to analyze genes that were previously predicted to be essential for melanoma surviving. Here we present the results of transient siRNA-mediated knockdown of the four of such genes, namely, UNC45A, STK11IP, RHPN2 and ZNFX1, in melanoma cell line A375, then assayed the cells for their viability, proliferation and ability to migrate in vitro. In our study, the knockdown of the genes predicted as essential for melanoma survival does not lead to statistically significant changes in cell viability. On the other hand, for each of the studied genes, mobility assays showed that the knockdown of each of the target genes accelerates the speed of cells migrating. Possible explanation for such counterintuitive results may include insufficiency of the predicting computational models or the necessity of a multiplex knockdown of the genes.AimsTo examine the hypothesis of essentiality of hypomutated genes for melanoma surviving we have performed knockdown of several genes in melanoma cell line and analyzed cell viability and their ability to migrate.MethodsKnockdown was performed by siRNAs transfected by Metafectene PRO. The levels of mRNAs before and after knockdown were evaluated by RT-qPCR analysis. Cell viability and proliferation were assessed by MTT assay. Cell migration was assessed by wound healing assay.ResultsThe knockdown of the genes predicted as essential for melanoma survival does not lead to statistically significant changes in cell viability. On the other hand, for each of the studied genes, mobility assays showed that the knockdown of each of the target genes accelerates the speed of cells migrating. ConclusionOur results do not confirm initial hypothesis that the genes predicted essential for melanoma survival as a matter of fact support the survival of melanoma cells.

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Section: Discussionmentioning

confidence: 99%

Analysis Of Candidate Genes Expected To Be Essential For Melanoma Surviving

Krivosheeva

Filatova

Moshkovskii

et al. 2020

Preprint

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show abstract

“…Zinc finger NFX1-type containing 1 (ZNFX1) encodes an interferon (IFN)-stimulated, mitochondrial-localized dsRNA sensor capable of restricting the replication of RNA viruses [38]. While its antiviral functions may not be relevant to the progression of human tumors, its antisense lncRNA ZFAS1 (zinc finger antisense 1) is well known for promoting growth of melanoma and other tumors [39].…”

Section: Discussionmentioning

confidence: 99%

Analysis of candidate genes expected to be essential for melanoma surviving

et al. 2020

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Introduction Cancers may be treated by selective targeting of the genes vital for their survival. A number of attempts have led to discovery of several genes essential for surviving of tumor cells of different types. In this work, we tried to analyze genes that were previously predicted to be essential for melanoma surviving. Here we present the results of transient siRNA-mediated knockdown of the four of such genes, namely, UNC45A, STK11IP, RHPN2 and ZNFX1, in melanoma cell line A375, then assayed the cells for their viability, proliferation and ability to migrate in vitro. In our study, the knockdown of the genes predicted as essential for melanoma survival does not lead to statistically significant changes in cell viability. On the other hand, for each of the studied genes, mobility assays showed that the knockdown of each of the target genes accelerates the speed of cells migrating. Possible explanation for such counterintuitive results may include insufficiency of the predicting computational models or the necessity of a multiplex knockdown of the genes. Aims To examine the hypothesis of essentiality of hypomutated genes for melanoma surviving we have performed knockdown of several genes in melanoma cell line and analyzed cell viability and their ability to migrate. Methods Knockdown was performed by siRNAs transfected by Metafectene PRO. The levels of mRNAs before and after knockdown were evaluated by RT-qPCR analysis. Cell viability and proliferation were assessed by MTT assay. Cell migration was assessed by wound healing assay. Results The knockdown of the genes predicted as essential for melanoma survival does not lead to statistically significant changes in cell viability. On the other hand, for each of the studied genes, mobility assays showed that the knockdown of each of the target genes accelerates the speed of cells migrating. Conclusion Our results do not confirm initial hypothesis that the genes predicted essential for melanoma survival as a matter of fact support the survival of melanoma cells.

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“…Recently zinc finger NFX1-type containing 1 (ZNFX1) was identified as a long dsRNA sensor that functions to sense viral RNA during the early stages of viral infection [159]. In A549 human lung adenocarcinoma and mouse embryonic fibroblast cells, ZNFX1 was found to display lower expression under steady state conditions but higher expression than the canonical dsRNA sensors RIG-I and MDA5.…”

Section: Zinc Finger Nfx1-type Containing 1 (Znfx1)mentioning

confidence: 99%

“…In A549 human lung adenocarcinoma and mouse embryonic fibroblast cells, ZNFX1 was found to display lower expression under steady state conditions but higher expression than the canonical dsRNA sensors RIG-I and MDA5. Under ligand-(HMW poly I:C) and IFN-stimulated conditions, ZNFX1 expression is drastically enhanced as an ISG [159]. ZNFX1 belongs to the SF1 helicase family that is highly conserved from fruit fly to human and contains an armadillo-type fold (ARM) domain, a P-loop helicase domain, and a zinc finger (ZF) domain [159].…”

Section: Zinc Finger Nfx1-type Containing 1 (Znfx1)mentioning

confidence: 99%

“…Under ligand-(HMW poly I:C) and IFN-stimulated conditions, ZNFX1 expression is drastically enhanced as an ISG [159]. ZNFX1 belongs to the SF1 helicase family that is highly conserved from fruit fly to human and contains an armadillo-type fold (ARM) domain, a P-loop helicase domain, and a zinc finger (ZF) domain [159]. ZNFX1 is a mitochondrion localized as a peripheral membrane protein that, upon sensing long dsRNA (or HMW poly I:C) through its ARM and P-loop domains, interacts with MAVS via ARM domain and promotes downstream induction of type I IFNs and ISGs in a RIG-I/MDA5-independent manner [160].…”

Section: Zinc Finger Nfx1-type Containing 1 (Znfx1)mentioning

confidence: 99%

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Avian Pattern Recognition Receptor Sensing and Signaling

Neerukonda

Katneni

2020

Veterinary Sciences

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Pattern recognition receptors (PRRs) are a class of immune sensors that play a critical role in detecting and responding to several conserved patterns of microorganisms. As such, they play a major role in the maintenance of immune homeostasis and anti-microbial defense. Fundamental knowledge pertaining to the discovery of PRR functions and their ligands continue to advance the understanding of immune system and disease resistance, which led to the rational design and/or application of various PRR ligands as vaccine adjuvants. In addition, the conserved nature of many PRRs throughout the animal kingdom has enabled the utilization of the comparative genomics approach in PRR identification and the study of evolution, structural features, and functions in many animal species including avian. In the present review, we focused on PRR sensing and signaling functions in the avian species, domestic chicken, mallard, and domestic goose. In addition to summarizing recent advances in the understanding of avian PRR functions, the present review utilized a comparative biology approach to identify additional PRRs, whose functions have been well studied in mammalians but await functional characterization in avian.

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Mitochondria-localised ZNFX1 functions as a dsRNA sensor to initiate antiviral responses through MAVS

Cited by 91 publications

References 50 publications

Analysis Of Candidate Genes Expected To Be Essential For Melanoma Surviving

Analysis Of Candidate Genes Expected To Be Essential For Melanoma Surviving

Analysis of candidate genes expected to be essential for melanoma surviving

Avian Pattern Recognition Receptor Sensing and Signaling

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