Adenosine-to-inosine (A-to-I) RNA editing is among the most prevalent RNA modifications in metazoans, catalyzed by enzymes known as adenosine deaminases acting on RNA (ADAR). ADAR enzymes bind to double-stranded RNA (dsRNA) and, through a deamination reaction, convert adenosine into inosine (Figure 1a) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10. The resulting inosine, similar to guanosine, forms base pairing with cytosine. Therefore, A-to-I RNA editing will alter the RNA structure and may recode proteins if it occurs within coding regions. The human transcriptome contains millions of RNA editing sites, with the majority situated in noncoding regions, particularly in introns and untranslated regions (UTRs) 11, 12. Most of the editing sites are located in repetitive sequences, primarily Alu elements in humans [12]. The inverted repetitive sequences form dsRNA structures to facilitate RNA editing [2].

Mammals possess two catalytically active ADAR proteins: ADAR1 and ADAR2. ADAR1 exhibits widespread expression, while ADAR2 is mainly expressed in the brain and artery [13]. Both ADAR proteins consist of multiple dsRNA-binding domains and a deaminase domain. ADAR1 has two isoforms, p110 and p150. Both isoforms have an additional Zβ domain, which is thought to be nonfunctional. Compared with ADAR1p110, ADAR1p150 includes an extra Zα domain. ADAR1p110 is constitutively expressed and localized in the nucleus, whereas ADAR1p150 can be induced by interferon (IFN) signaling and is predominantly localized in the cytoplasm (Figure 1b).