ArticleNucleic acids research2014
siRNA enhances DNA-mediated interferon lambda-1 response through crosstalk between RIG-I and IFI16 signalling pathway.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
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- A DNA Pull-Down Assay with Diversity Forms of Competitor for Detecting or Evaluating Protein-DNA Interactions.Methods in molecular biology (Clifton, N.J.) · 2023Article
- IFI16 directly senses viral RNA and enhances RIG-I transcription and activation to restrict influenza virus infection.Nature microbiology · 2021Article
- Cytoplasmic-translocated Ku70 senses intracellular DNA and mediates interferon-lambda1 induction.Immunology · 2021Article
- MicroRNA Profiles in Monocyte-Derived Macrophages Generated by Interleukin-27 and Human Serum: Identification of a Novel HIV-Inhibiting and Autophagy-Inducing MicroRNA.International journal of molecular sciences · 2021Article
- Activation and Immune Regulation Mechanisms of PYHIN Family During Microbial Infection.Frontiers in microbiology · 2021Review
- Baculovirus Transduction in Mammalian Cells Is Affected by the Production of Type I and III Interferons, Which Is Mediated Mainly by the cGAS-STING Pathway.Journal of virology · 2020Article
- Zika Virus-Induction of the Suppressor of Cytokine Signaling 1/3 Contributes to the Modulation of Viral Replication.Pathogens (Basel, Switzerland) · 2020Article
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- Crosstalk between Cytoplasmic RIG-I and STING Sensing Pathways.Trends in immunology · 2017Review
- Rearrangement of mitochondrial pyruvate dehydrogenase subunit dihydrolipoamide dehydrogenase protein-protein interactions by the MDM2 ligand nutlin-3.Proteomics · 2016Article
- The unique regulation and functions of type III interferons in antiviral immunity.Current opinion in virology · 2015Review
- Nanotherapy for Cancer: Targeting and Multifunctionality in the Future of Cancer Therapies.ACS biomaterials science & engineering · 2015Review
- RNA interference approaches for treatment of HIV-1 infection.Genome medicine · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
In addition to silencing specific genes, small interfering RNA (siRNA) transfection is also associated with the non-specific induction of inflammatory cytokines and type I interferon. Those so-called "off-target" effects have considerable implications for the interpretation of in vitro studies and clinical application of siRNA. The present study attempted to develop a better understanding of the mechanism involved in these off target effects. Synthesized siRNA significantly enhances DNA-mediated interferon lambda-1 response (IFN-λ1/IL-29), a newly characterized antiviral interferon in non-immune or primary immune cells. This enhancement was most pronounced by double-stranded siRNA with at least a 2-nucleotide overhang at one 3' terminus in a dose-dependent manner, while the presence of DNA was indispensable. A pull-down assay using biotinylated siRNA- or DNA-conjugated beads indicated that retinoic acid-inducible gene I (RIG-I) and interferon gamma-inducible protein 16 (IFI16) were involved in the sensing of siRNA and DNA, respectively. Co-immunoprecipitation analysis further revealed that RIG-I and IFI16 formed a complex via siRNA, and the dissociation of IFI16 from this complex in the presence of DNA activated the downstream STING-TBK1-IRF3 (stimulator of interferon genes - tank-binding kinase 1 - interferon regulatory factor 3) pathway, shedding light on a new physiological signalling pathway to activate innate immunity. Collectively, these findings may provide rational information for siRNA-induced innate immunity, with important implications for developing siRNA-based reagents to control human diseases.
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