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All I's on the RADAR: role of ADAR in gene regulation

Adenosine to inosine (A‐to‐I) editing is the most abundant form of RNA modification in mammalian cells, which is catalyzed by adenosine deaminase acting on the double‐stranded RNA (ADAR) protein family. A‐to‐I editing is currently known to be involved in the regulation of the immune system, RNA splicing, protein recoding, microRNA biogenesis, and formation of heterochromatin. Editing occurs within regions of double‐stranded RNA, particularly within inverted Alu repeats, and is associated with many diseases including cancer, neurological disorders, and metabolic syndromes. However, the significance of RNA editing in a large portion of the transcriptome remains unknown. Here, we review the current knowledge about the prevalence and function of A‐to‐I editing by the ADAR protein family, focusing on its role in the regulation of gene expression. Furthermore, RNA editing‐independent regulation of cellular processes by ADAR and the putative role(s) of this process in gene regulation will be discussed.