ADAR

The double-stranded RNA-specific adenosine deaminase enzyme family are encoded by the ADAR family genes. ADAR stands for adenosine deaminase acting on RNA. This article focuses on the ADAR proteins; This article details the evolutionary history, structure, function, mechanisms and importance of all proteins within this family.

ADAR enzymes bind to double-stranded RNA (dsRNA) and convert adenosine to inosine (hypoxanthine) by deamination. ADAR proteins act post-transcriptionally, changing the nucleotide content of RNA. The conversion from adenosine to inosine (A to I) in the RNA disrupts the normal A:U pairing, destabilizing the RNA. Inosine is structurally similar to guanine (G) which leads to inosine to cytosine (I:C) binding. Inosine typically mimics guanosine during translation but can also bind to uracil, cytosine, and adenosine, though it is not favored.

Codon changes may arise from RNA editing leading to changes in the coding sequences for proteins and their functions. Most editing sites are found in noncoding regions of RNA such as untranslated regions (UTRs), Alu elements, and long interspersed nuclear elements (LINEs). Codon changes can give rise to alternate transcriptional splice variants. ADAR impacts the transcriptome in editing-independent ways, likely by interfering with other RNA-binding proteins.

Mutations in this gene are associated with several diseases including HIV, measles, and melanoma. Recent research supports a linkage between RNA-editing and nervous system disorders such as amyotrophic lateral sclerosis (ALS). Atypical RNA editing linked to ADAR may also correlate to mental disorders such as schizophrenia, epilepsy, and suicidal depression.