ADAR1: Beyond Just an RNA Editor

The RNA editing enzyme adenosine deaminase acting on RNA 1 (ADAR1) has recently emerged from relative obscurity to be recognized as a key player in a variety of inflammatory diseases, including cancer. This growing recognition has generated interest in developing ADAR1 inhibitors; however, several fundamental questions about the enzyme need to be answered before ADAR1-based therapies can be successful. In this review, we summarize the current understanding of ADAR1, including its protein structure, RNA substrates, and roles in both innate and adaptive immunity. Recent studies have shed light on ADAR1 protein interactions and its RNA editing–independent functions. We also explore the involvement of ADAR1 in human diseases, with a focus on its roles in various cancers. Drosophila lacks an ADAR1 homolog; instead, the ADAR2 homolog is responsible for editing double-stranded RNA to prevent aberrant activation of the innate immune system. Finally, we address major questions in the field that still remain unanswered.