Distinct interactomes of ADAR1 nuclear and cytoplasmic protein isoforms and their responses to interferon induction.

Autor:	Vukić D; Central European Institute of Technology (CEITEC), Masaryk University, Kamenice 5, Brno 62500, Czechia.; NationalCentre for Biomolecular Research, Faculty of Science, Masaryk University, Kamenice 5, Brno 62500, Czechia., Cherian A; Central European Institute of Technology (CEITEC), Masaryk University, Kamenice 5, Brno 62500, Czechia.; NationalCentre for Biomolecular Research, Faculty of Science, Masaryk University, Kamenice 5, Brno 62500, Czechia., Keskitalo S; Institute of Biotechnology, HelsinkiInstitute of Life Science (HiLIFE), University of Helsinki, Helsinki 00014, Finland., Bong YT; Institute of Biotechnology, HelsinkiInstitute of Life Science (HiLIFE), University of Helsinki, Helsinki 00014, Finland., Marônek M; Central European Institute of Technology (CEITEC), Masaryk University, Kamenice 5, Brno 62500, Czechia., Yadav L; Institute of Biotechnology, HelsinkiInstitute of Life Science (HiLIFE), University of Helsinki, Helsinki 00014, Finland., Keegan LP; Central European Institute of Technology (CEITEC), Masaryk University, Kamenice 5, Brno 62500, Czechia., Varjosalo M; Institute of Biotechnology, HelsinkiInstitute of Life Science (HiLIFE), University of Helsinki, Helsinki 00014, Finland., O'Connell MA; Central European Institute of Technology (CEITEC), Masaryk University, Kamenice 5, Brno 62500, Czechia.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2024 Dec 11; Vol. 52 (22), pp. 14184-14204.
DOI:	10.1093/nar/gkae1106
Abstrakt:	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. (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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