Nejvíce citovaný článek - PubMed ID 34634806
The comprehensive interactomes of human adenosine RNA methyltransferases and demethylases reveal distinct functional and regulatory features
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