Abstract
Adenosine to inosine conversion by adenosine deaminases acting on RNA (ADARs) was first identified in the late 1980s of the previous century. As the conversion of adenosines to inosines can be easily detected by sequencing of cDNAs, where the presence of an inosine reads out as a guanosine, the analysis of this type of RNA editing has become widespread. Consequently, several pipelines for detecting inosines in transcriptomes have become available. Still, how to interpret the consequences and alterations of RNA-editing events in whole transciptome editomes is a matter of debate. In particular, the cause or consequence of altered editomes on disease development is poorly understood. Similarly, absolute frequencies of editing events in single molecules, their longitudinal distribution, and naturally occurring changes during development, in different tissues, or in response to physiological changes need to be explored. Lastly, while the use of site-directed RNA editing as a treatment of certain genetic diseases is rapidly evolving, the applicability of this technology still faces several technical obstacles. In this review, we describe the current state of knowledge on adenosine deamination-type RNA editing, its involvement in disease development, and its potential as a therapeutic. Lastly, we highlight open challenges and questions that need to be addressed.