Adenosine deaminase acting on RNA 2 (ADAR2)

Adenosine deaminase acting on RNA 2 (ADAR2) is a member of the ADAR family of enzymes responsible for the post-transcriptional conversion of adenosine to inosine (A-to-I) within double-stranded RNA regions [1, 3]. This process, known as RNA editing, is a critical mechanism for diversifying the proteome and regulating gene expression, particularly in the central nervous system where ADAR2 mediates the essential Q/R site editing of the GluA2 subunit of AMPA receptors [5, 12]. Dysregulation of ADAR2 is implicated in several severe pathologies; for instance, the loss of ADAR2 activity in motor neurons is a hallmark of sporadic amyotrophic lateral sclerosis (ALS), leading to calcium-permeable AMPA receptors and excitotoxic cell death [6, 8]. In oncology, ADAR2 often functions as a tumor suppressor, and its downregulation is observed in glioblastoma and hepatocellular carcinoma, where it fails to edit transcripts that normally limit cell proliferation [11, 13]. Therapeutically, ADAR2 is being explored as both a target for small molecule inhibition in specific cancers and as a tool for site-directed RNA editing [2, 10]. Emerging RNA-editing platforms aim to recruit endogenous ADAR2 using engineered guide RNAs to correct point mutations at the transcript level, offering a potentially reversible and safer alternative to DNA-based genome editing [5, 16].

Other names

ADARB1RED1DRADA2DRABA2RNA-editing enzyme 1Double-stranded RNA-specific editase 1Adenosine deaminase RNA-specific B1

ADAR2 catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA). Therapeutic strategies involve either the inhibition of this catalytic activity using small molecule purine analogs or the recruitment of endogenous ADAR2 via antisense oligonucleotides (guide RNAs) for site-directed RNA editing to correct pathogenic mutations.