Deciphering the functions and regulation of brain-enriched A-to-I RNA editing

Adenosine-to-inosine (A-to-I) RNA editing, in which genomically encoded adenosine is changed to inosine in RNA, is catalyzed by adenosine deaminase acting on RNA (ADAR). This fine-tuning mechanism is critical during normal development and diseases, particularly in relation to brain functions. A-to-I RNA editing has also been hypothesized to be a driving force in human brain evolution. A large number of RNA editing sites have recently been identified, mostly as a result of the development of deep sequencing and bioinformatic analyses. Deciphering the functional consequences of RNA editing events is challenging, but emerging genome engineering approaches may expedite new discoveries. To understand how RNA editing is dynamically regulated, it is imperative to construct a spatiotemporal atlas at the species, tissue and cell levels. Future studies will need to identify the cis and trans regulatory factors that drive the selectivity and frequency of RNA editing. We anticipate that recent technological advancements will aid researchers in acquiring a much deeper understanding of the functions and regulation of RNA editing.