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

RNA editing is one of the most prevalent and abundant forms of post-transcriptional RNA modification observed in normal physiological processes and often aberrant in diseases including cancer. RNA editing changes the sequences of mRNAs, making them different from the source DNA sequence. Edited mRNAs can produce editing-recoded protein isoforms that are functionally different from the corresponding genome-encoded protein isoforms. The major type of RNA editing in mammals occurs by enzymatic deamination of adenosine to inosine (A-to-I) within double-stranded RNAs (dsRNAs) or hairpins in pre-mRNA transcripts. Enzymes that catalyse these processes belong to the adenosine deaminase acting on RNA (ADAR) family. The vast majority of knowledge on the RNA editing landscape relevant to human disease has been acquired using in vitro cancer cell culture models. The limitation of such in vitro models, however, is that the physiological or disease relevance of results obtained is not necessarily obvious. In this review we focus on discussing in vivo occurring RNA editing events that have been identified in human cancer tissue using samples surgically resected or clinically retrieved from patients. We discuss how RNA editing events occurring in tumours in vivo can identify pathological signalling mechanisms relevant to human cancer physiology which is linked to the different stages of cancer progression including initiation, promotion, survival, proliferation, immune escape and metastasis.

• Klíčová slova
• ADARs, RNA editing, RNA editing in cancer, cancer development,
• MeSH
• adenosin genetika   MeSH
• dvouvláknová RNA genetika   MeSH
• editace RNA * MeSH
• inosin genetika   MeSH
• karcinogeneze genetika   patologie   MeSH
• lidé MeSH
• nádory genetika   metabolismus   patologie   MeSH
• proteiny vázající RNA genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• adenosin MeSH
• dvouvláknová RNA MeSH
• inosin MeSH
• proteiny vázající RNA MeSH