RNA-sensing pathways play a pivotal role in host defense against pathogenic infections to maintain cellular homeostasis. However, in the absence of infection, certain endogenous RNAs can serve as the activators of RNA-sensing pathways as well. The inappropriate activation of RNA-sensing pathways by self-ligands leads to systemic inflammation and autoimmune diseases. In this review, we summarize current findings on the sterile activation of RNA sensors, as well as its implications in autoimmunity, inflammatory diseases, and therapeutics.
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http://dx.doi.org/10.1093/jmcb/mjae029 | DOI Listing |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11659683 | PMC |
Mol Cell
December 2024
Department of Cell Biology, Cancer Institute, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan. Electronic address:
Viral mimicry driven by endogenous double-stranded RNA (dsRNA) stimulates innate and adaptive immune responses. However, the mechanisms that regulate dsRNA-forming transcripts during cancer therapy remain unclear. Here, we demonstrate that dsRNA is significantly accumulated in cancer cells following pharmacologic induction of micronuclei, stimulating mitochondrial antiviral signaling (MAVS)-mediated dsRNA sensing in conjunction with the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway.
View Article and Find Full Text PDFSmall Methods
December 2024
Aier Eye Hospital, Jinan University, Guangzhou, 510071, China.
In the realms of bioengineering and biopharmaceuticals, there exists a critical demand for advanced genetic tools that can interact with specific cell signaling pathways to accurately identify and target various cell types. This research introduces the innovative CRISPR-ADAReader system, which enables precise manipulation of cell activity through sensing target RNA. Featuring both positive and negative feedback loops, the system allows for tailored regulation across different cell types in response to various internal signals, showcasing exceptional programmability, specificity, and sensitivity.
View Article and Find Full Text PDFInt J Mol Med
January 2025
Hospital of Stomatology, Sun Yat‑sen University, Guangzhou, Guangdong 510060, P.R. China.
Cell senescence impedes the self‑renewal and osteogenic capacity of bone marrow mesenchymal stem cells (BMSCs), thus limiting their application in tissue regeneration. The present study aimed to elucidate the role and mechanism of repetitive element (RE) activation in BMSC senescence and osteogenesis, as well as the intervention effect of quercetin. In an H2O2‑induced BMSC senescence model, quercetin treatment alleviated senescence as shown by a decrease in senescence‑associated β‑galactosidase (SA‑β‑gal)‑positive cell ratio, increased colony formation ability and decreased mRNA expression of p21 and senescence‑associated secretory phenotype genes.
View Article and Find Full Text PDFJ Gen Virol
October 2024
Department of Microbial Sciences, University of Surrey, Guildford, GU2 7XH, UK.
Poxviruses are dsDNA viruses infecting a wide range of cell types, where they need to contend with multiple host antiviral pathways, including DNA and RNA sensing. Accordingly, poxviruses encode a variety of immune antagonists, most of which are expressed early during infection from within virus cores before uncoating and genome release take place. Amongst these antagonists, the poxvirus immune nuclease (poxin) counteracts the cyclic 2'3'-GMP-AMP (2'3'-cGAMP) synthase (cGAS)/stimulator of interferon genes DNA sensing pathway by degrading the immunomodulatory cyclic dinucleotide 2'3'-cGAMP, the product of activated cGAS.
View Article and Find Full Text PDFAging Cell
September 2024
Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry, and Biomedical Sciences, Queen's University Belfast, Belfast, UK.
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