Adenosine deaminase RNA-specific B1 (ADAR2) (ADAR2)

Adenosine deaminase RNA-specific B1 (ADAR2), also known as Double-stranded RNA-specific editase 1, is a critical enzyme that catalyzes the post-transcriptional conversion of adenosine to inosine (A-to-I) within double-stranded RNA (dsRNA) [1, 2]. This RNA editing process is essential for generating molecular diversity, as inosine is recognized as guanosine by the cellular machinery, leading to amino acid substitutions and altered RNA processing [8, 10]. ADAR2 is primarily expressed in the central nervous system, where its most vital function is the site-specific editing of the GRIA2 (GluA2) subunit of AMPA receptors; this editing at the Q/R site is necessary to prevent calcium permeability and subsequent excitotoxic neuronal death [11, 12]. Pathologically, the loss or downregulation of ADAR2 activity is strongly linked to neurodegenerative conditions such as Amyotrophic Lateral Sclerosis (ALS) and certain forms of epilepsy, as well as the progression of malignant tumors like glioblastoma [13, 19]. In the context of drug development, ADAR2 is not only a target for restoration in neurodegeneration but also a key effector for novel RNA-editing therapeutics, such as ADAR-recruiting oligonucleotides, which aim to correct genetic mutations in vivo [13, 15]. While no small-molecule inhibitors or activators are currently FDA-approved, research is ongoing to develop selective modulators and delivery systems for RNA-based tools [3, 13]. Therapeutic challenges include the potential for widespread off-target editing and the risk of disrupting essential brain functions, making precise targeting and safety monitoring critical [11, 15]. The enzyme requires inositol hexakisphosphate (IP6) as a buried cofactor for its catalytic activity, which has been a focus for structural studies and drug design [19].

Other names

ADARB1RED1DRADA2Double-stranded RNA-specific editase 1RNA-editing deaminase 1RNA-editing enzyme 1dsRNA adenosine deaminase

Hydrolytic deamination of adenosine to inosine in double-stranded RNA