Illuminating spatial A-to-I RNA editing signatures within the Drosophila brain

Abstract

SummaryAdenosine-to-inosine (A-to-I) RNA editing, catalyzed by ADAR enzymes, is a ubiquitous mechanism that generates transcriptomic diversity. This process is particularly important for proper neuronal function; however, little is known about how RNA editing is dynamically regulated between the many functionally distinct neuronal populations of the brain. In this resource paper, we present a spatial RNA editing map in the Drosophila brain and show that different neuronal populations possess distinct RNA editing signatures. After purifying and sequencing RNA from genetically marked neuronal nuclei, we identified a large number of novel editing sites and compared editing levels in hundreds of transcripts across nine functionally different neuronal populations. We found distinct editing repertoires for each population, including novel sites in repeat regions of the transcriptome and differential editing in highly conserved and likely functional regions of transcripts that encode essential neuronal genes. These changes are site-specific and not driven by changes in Adar expression, suggesting a complex, targeted regulation of editing levels in key transcripts. This fine-tuning of the transcriptome between different neurons by RNA editing may account for functional differences between distinct populations in the brain.\n\nSignificance StatementA fundamental question in contemporary neuroscience is how the remarkable cellular diversity required for the intricate function of the nervous system is achieved. In this manuscript, we bridge the gap between a cellular machinery that is known to diversify the transcriptome and the existence of distinct neuronal populations that compose Drosophila brain. Adenosine-to-inosine (A-to-I) RNA-editing is a ubiquitous mechanism that generates transcriptomic diversity in cells by recoding certain adenosines within the pre-mRNA sequence into inosines. We present a spatial map of RNA editing across different neuronal populations in Drosophila brain. Each neuronal population has a distinct editing signature, with the majority of differential editing occurring in highly conserved regions of transcripts that encode ion channels and other essential neuronal genes.