NCBI Summary:
DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein that is upregulated in response to treatment with beta-interferon and a protein kinase C-activating compound, mezerein. Irreversible reprogramming of melanomas can be achieved by treatment with both these agents; treatment with either agent alone only achieves reversible differentiation. Genetic variation in this gene is associated with diabetes mellitus insulin-dependent type 19. [provided by RefSeq, Jul 2012]
General function
Receptor, RNA processing
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Cellular localization
Cytoplasmic, Plasma membrane
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Ovarian function
Steroid metabolism
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Polyinosinic-Polycytidylic Acid Initiates Ovarian Innate Antiviral Response and Inhibits Steroidogenesis in Female Mice. Yan K 2013 et al.
Viral infection may perturb ovarian functions. However, innate antiviral response in the ovary has not been intensively investigated. In this study, we examined the innate antiviral system in the mouse ovary and the impacts of antiviral response on steroidogenesis. Major virus sensors, including Toll-like receptor 3 (TLR3), retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5), are predominantly expressed in ovarian stromal and granulosa cells. Polyinosinic-polycytidylic acid [poly(I:C)] is a common agonist of TLR3, MDA5, and RIG-I. Intraperitoneal injection of poly(I:C) activated nuclear factor kappa B and interferon (IFN) regulatory factor 3 in the ovarian cells, and induced the expression of pro-inflammatory cytokines, including tumor necrosis factor alpha, interleukin 6, and type 1 interferons (IFNA/B). Moreover, poly(I:C) upregulated the expression of several antiviral proteins, including 2'-5'-oligoadenylate synthetase, IFN-stimulated gene 15, and Mx GTPase 1. The innate antiviral response in the ovary was significantly reduced in Tlr3-deficient mice. Notably, we demonstrated that poly(I:C) injection inhibits steroidogenesis enzyme expression and decreases plasma estradiol and testosterone levels. Results show that the mouse ovary is equipped with innate antiviral state, and the antiviral response perturbs ovarian endocrine function.
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Expression regulated by
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Ovarian localization
Granulosa
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Toll-like receptor 3 and RIG-I-like receptor activation induces innate antiviral responses in mouse ovarian granulosa cells. Yan K et al. Viral infections of the ovary can cause pathological conditions. However, innate antiviral responses in the ovary are poorly understood. In this study, we demonstrate that Toll-like receptor 3 (TLR3), retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) are constitutively expressed in the mouse ovary and predominantly located in granulosa cells. Polyinosinic-polycytidylic acid [poly(I:C)], a common agonist of TLR3, MDA5 and RIG-I, induced innate antiviral responses in ovarian granulosa cells. Poly(I:C) up-regulated pro-inflammatory cytokines, including TNF-a and IL-6, and type I interferons (IFN-a/?. Moreover, poly(I:C) induced the expression of antiviral proteins, including 2'-5'-oligoadenylate synthetase, Mx GTPase 1 and IFN-stimulating gene 15, in granulosa cells. In contrast, P450 aromatase expression was inhibited by poly(I:C). The poly(I:C)-induced antiviral responses in TLR3 knockout (TLR3(-/-)) ovarian granulosa cells were reduced, and completely abolished by blocking of MDA5/RIG-I signaling. Further, the poly(I:C)-induced cytokine expression in TLR3(-/-) cells was reduced by knockdown of MDA5 or RIG-I. Data suggest that TLR3, MDA5 and RIG-I cooperate in mediating innate antiviral responses in granulosa cells, which may contribute to the defense of the ovary against viral infections.