Comprehensive identification of edited miRNAs in the human brain

A-to-I editing modifies RNA transcripts from their genomic blueprint. A prerequisite for this process is a double-stranded RNA (dsRNA) structure. Such dsRNAs are formed as part of the micro-RNA (miRNA) maturation process, and it is therefore expected that miRNAs are affected by A-to-I editing. Editing of miRNAs has the potential to add another layer of complexity to gene regulation pathways, especially if editing occurs within the miRNA recognition site. Thus, it is of interest to study the extent of this phenomenon. Current reports in the literature disagree on its extent; while some reports claim that it may be widespread others deem the reported events as rare. Utilizing a next-generation sequencing approach supplemented by an extensive bioinformatic analysis, we were able to systematically identify A-to-I editing events in mature miRNAs derived from human brain tissue. Our algorithm successfully identified many of the known editing sites in mature miRNAs, and revealed additional novel sites, six of which are in the recognition sites of the miRNAs. The editing efficiency of most sites identified is very low. Thus, we find that A-to-I editing does alter several miRNAs but it is not widespread.