The RNA editing enzyme adenosine deaminase acting on RNA 1 (ADAR1) is essential for correct functioning of innate immune responses. The ADAR1p110 isoform is mainly nuclear and ADAR1p150, which is interferon (IFN) inducible, is predominately cytoplasmic. Using three different methods - co-immunoprecipitation (co-IP) of endogenous ADAR1, Strep-tag co-IP and BioID with individual ADAR1 isoforms - a comprehensive interactome was generated during both homeostasis and the IFN response. Both known and novel interactors as well as editing regulators were identified. Nuclear proteins were detected as stable interactors with both ADAR1 isoforms. In contrast, BioID identified distinct protein networks for each ADAR1 isoform, with nuclear components observed with ADAR1p110 and components of cytoplasmic cellular condensates with ADAR1p150. RNase A digestion distinguished between distal and proximal interactors, as did a double-stranded RNA (dsRNA)-binding mutant of ADAR1 which demonstrated the importance of dsRNA binding for ADAR1 interactions. IFN treatment did not affect the core ADAR1 interactomes but resulted in novel interactions, the majority of which are proximal interactions retained after RNase A treatment. Short treatment with high molecular weight poly(I:C) during the IFN response resulted in dsRNA-binding-dependent changes in the proximal protein network of ADAR1p110 and association of the ADAR1p150 proximal protein network with some components of antiviral stress granules.

• MeSH
• adenosindeaminasa * metabolismus   genetika   MeSH
• buněčné jádro * metabolismus   MeSH
• cytoplazma * metabolismus   MeSH
• dvouvláknová RNA metabolismus   genetika   MeSH
• editace RNA MeSH
• HEK293 buňky MeSH
• HeLa buňky MeSH
• interferony metabolismus   genetika   MeSH
• lidé MeSH
• mapy interakcí proteinů MeSH
• poly I-C farmakologie   MeSH
• protein - isoformy * metabolismus   genetika   MeSH
• proteiny vázající RNA * metabolismus   genetika   MeSH
• vazba proteinů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ADAR protein, human MeSH Prohlížeč
• adenosindeaminasa * MeSH
• dvouvláknová RNA MeSH
• interferony MeSH
• poly I-C MeSH
• protein - isoformy * MeSH
• proteiny vázající RNA * MeSH

Although the immunomodulatory properties of prebiotics were demonstrated many years ago in poultry, not all mechanisms of action are yet clear. Dendritic cells (DCs) are the main antigen-presenting cells orchestrating the immune response in the chicken gastrointestinal tract, and they are the first line of defense in the immune response. Despite the crucial role of DCs in prebiotic immunomodulatory properties, information is lacking about interaction between prebiotics and DCs in an avian model. Mannan-oligosaccharides, β-glucans, fructooligosaccharides, and chitosan-oligosaccharides are the main groups of prebiotics having immunomodulatory properties. Because pathogen-associated molecular patterns on these prebiotics are recognized by many receptors of DCs, prebiotics can mimic activation of DCs by pathogens. Short-chain fatty acids are products of prebiotic fermentation by microbiota, and their anti-inflammatory properties have also been demonstrated in DCs. This review summarizes current knowledge about avian DCs in the gastrointestinal tract, and for the first-time, their role in the immunomodulatory properties of prebiotics within an avian model.

• Klíčová slova
• antigen-presenting cell, avian dendritic cells, chicken, pattern recognition receptors, prebiotic,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH