title: Systematic identification of edited microRNAs in the human brain.
abstract: Adenosine-to-inosine (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 microRNA (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-mRNA 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 (NGS) 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 tissues. Our algorithm successfully identified many of the known editing sites in mature miRNAs and revealed 17 novel human sites, 12 of which are in the recognition sites of the miRNAs. We confirmed most of the editing events using in vitro ADAR overexpression assays. The editing efficiency of most sites identified is very low. Similar results are obtained for publicly available data sets of mouse brain-regions tissues. Thus, we find that A-to-I editing does alter several miRNAs, but it is not widespread.
authors.affiliation: Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel.
authors.forename: Shahar
authors.initials: S
authors.lastname: Alon
authors.forename: Eyal
authors.initials: E
authors.lastname: Mor
authors.forename: Francois
authors.initials: F
authors.lastname: Vigneault
authors.forename: George M
authors.initials: GM
authors.lastname: Church
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Federica
authors.initials: F
authors.lastname: Galeano
authors.forename: Angela
authors.initials: A
authors.lastname: Gallo
authors.forename: Noam
authors.initials: N
authors.lastname: Shomron
authors.forename: Eli
authors.initials: E
authors.lastname: Eisenberg
mesh_terms: D000241:Adenosine / Q000235:genetics / Q000378:metabolism*; D000243:Adenosine Deaminase / Q000235:genetics / Q000378:metabolism; D000465:Algorithms; D001921:Brain / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods*; D030541:Databases, Genetic; D015894:Genome, Human; D006801:Humans; D007288:Inosine / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D017393:RNA Editing; D016601:RNA-Binding Proteins; D017423:Sequence Analysis, RNA / Q000379:methods
chemical_list: D035683:MicroRNAs; D016601:RNA-Binding Proteins; D007288:Inosine; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase; D000241:Adenosine