Activity regulation of adenosine deaminases acting on RNA (ADARs)

Adenosine deaminases acting on RNA (ADARs) are the enzymes that are responsible for the A to I RNA editing process in mammals, which is an important mechanism that increases molecular diversity. A to I RNA editing consists of an enzymatic conversion of specific adenosine in pre-mRNA, leading to alteration of the properties of both the RNA itself and the translated protein. Currently, the importance of this phenomenon is increasingly recognized as it affects a diverse set of cellular pathways. ADAR function within the cell, especially in the neurons, is to diversify the features of a limited set of unique transcripts, mostly neurotransmitter receptors; however, a growing set of target is going to be discovered, increasing the importance of the RNA editing event in the proper physiology of the cell. Despite the functional relevance of these enzymes, there is a gap of knowledge in the mechanisms that regulate ADAR activity and consequently about the modulation of RNA editing process. This review summarizes ongoing investigations of ADAR regulation at the transcriptional, post-transcriptional and post-translational level and addresses new hypothetical mechanisms that are capable of modulating ADAR activity, including subcellular localization, dimerization and interaction with trans-acting factors.