The role of ADAR1 in the Mobility and Metabolic adaptation

Abstract

RNA editing is a well-known post-transcriptional event and deamination is one of the major processes. There are two types of deamination of RNA: cytidine to uridine and adenosine to inosine. The A-to-I transition is edited by ADAR1 (Adenosine Deaminase, RNA Acting on RNA), which recognizes double-stranded RNA. A to I RNA deamination occurs primarily at the Alu repeats and functionally at the 3'UTR region, coding sequence, and microRNA precursors. This can result in recoding of a target gene or alter its expression and function. Recent studies suggested the novel role of ADAR1 in the treatment of human cancers, including epigenetic therapy and immunotherapy. We aimed to find out the role of ADAR1 in human breast cancer cells by combined analysis of RNA seq and cellular analysis after ADAR1 depletion. As a result, we found the depletion of ADAR1 suppresses the expression of ARPIN in an editing-independent manner. As the ARPIN inhibits the branching of actin filaments, the ADAR1 depletion stimulated cell mobility. On the other hand, we revealed the role of ADAR1 in the glucose-limiting condition. Specifically, when ADAR1 was depleted, we found an enhanced autophagic response and increased viability of breast cancer cells. This response seems to be triggered by activated AMPK that subsequently activated Beclin-1 and LC3. Altogether, these results present a new role of ADAR1 in breast cancer.