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.