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      MiRNAs and lncRNAs in the regulation of innate immune signaling

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          Abstract

          The detection and defense against foreign agents and pathogens by the innate immune system is a crucial mechanism in the body. A comprehensive understanding of the signaling mechanisms involved in innate immunity is essential for developing effective diagnostic tools and therapies for infectious diseases. Innate immune response is a complex process involving recognition of pathogens through receptors, activation of signaling pathways, and cytokine production, which are all crucial for deploying appropriate countermeasures. Non-coding RNAs (ncRNAs) are vital regulators of the immune response during infections, mediating the body's defense mechanisms. However, an overactive immune response can lead to tissue damage, and maintaining immune homeostasis is a complex process in which ncRNAs play a significant role. Recent studies have identified microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) as key players in controlling gene expression in innate immune pathways, thereby participating in antiviral defenses, tumor immunity, and autoimmune diseases. MiRNAs act by regulating host defense mechanisms against viruses, bacteria, and fungi by targeting mRNA at the post-transcriptional level, while lncRNAs function as competing RNAs, blocking the binding of miRNAs to mRNA. This review provides an overview of the regulatory role of miRNAs and lncRNAs in innate immunity and its mechanisms, as well as highlights potential future research directions, including the expression and maturation of new ncRNAs and the conservation of ncRNAs in evolution.

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          Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway.

          The presence of DNA in the cytoplasm of mammalian cells is a danger signal that triggers host immune responses such as the production of type I interferons. Cytosolic DNA induces interferons through the production of cyclic guanosine monophosphate-adenosine monophosphate (cyclic GMP-AMP, or cGAMP), which binds to and activates the adaptor protein STING. Through biochemical fractionation and quantitative mass spectrometry, we identified a cGAMP synthase (cGAS), which belongs to the nucleotidyltransferase family. Overexpression of cGAS activated the transcription factor IRF3 and induced interferon-β in a STING-dependent manner. Knockdown of cGAS inhibited IRF3 activation and interferon-β induction by DNA transfection or DNA virus infection. cGAS bound to DNA in the cytoplasm and catalyzed cGAMP synthesis. These results indicate that cGAS is a cytosolic DNA sensor that induces interferons by producing the second messenger cGAMP.
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            The microbiome and innate immunity.

            The intestinal microbiome is a signalling hub that integrates environmental inputs, such as diet, with genetic and immune signals to affect the host's metabolism, immunity and response to infection. The haematopoietic and non-haematopoietic cells of the innate immune system are located strategically at the host-microbiome interface. These cells have the ability to sense microorganisms or their metabolic products and to translate the signals into host physiological responses and the regulation of microbial ecology. Aberrations in the communication between the innate immune system and the gut microbiota might contribute to complex diseases.
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              Toll-like Receptors and the Control of Immunity

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                Author and article information

                Contributors
                Journal
                Noncoding RNA Res
                Noncoding RNA Res
                Non-coding RNA Research
                KeAi Publishing
                2468-0540
                01 August 2023
                December 2023
                01 August 2023
                : 8
                : 4
                : 534-541
                Affiliations
                [a ]Bashkir State Medical University, Ufa, Republic of Bashkortostan, 450008, Russia
                [b ]Department of Neurosurgery, Рeoples’ Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya Street, Moscow, 117198, Russian Federation
                [c ]Traumatology and Orthopedics Center, Central Clinical Hospital of the Russian Academy of Sciences, 117593, Moscow, Russia
                [d ]Department of Neurosurgery, Smolensk State Medical University of the Ministry of Health of the Russian Federation, Smolensk, Russia
                [e ]Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China
                Author notes
                []Corresponding author. ilgiz_gareev@ 123456mail.ru
                Article
                S2468-0540(23)00047-1
                10.1016/j.ncrna.2023.07.002
                10410465
                37564295
                476eb4ff-70a0-4975-b86d-f3eb2e481b95
                © 2023 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 28 July 2023
                : 31 July 2023
                Categories
                Review Article

                innate immune,ncrnas,mirnas,lncrnas,regulation
                innate immune, ncrnas, mirnas, lncrnas, regulation

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