microRNA editing in autistic brains

Autism Spectrum Disorder (ASD) is a group of neurodevelopmental disorders, characterized by deficits in reciprocal interaction and repetitive behaviors. Although ASD is one of the most heritable disorders, the cause of most cases remains largely unknown. By orchestrating neurodevelopmental gene expression, miRNA are central regulators of brain development. In light of their double stranded nature, miRNA serve as prime substrates for adenosine deaminase acting on RNA (ADAR) enzymes. ADAR-mediated A-to-I editing of mRNA was recently shown to play a role in ASD. However, the role of miRNA editing in the disorder remains to be elucidated. Understanding the contribution of miRNA editing to ASD is essential for mapping the molecular networks underlying ASD.

Toward this goal, we examined A-to-I editing of known miRNA in postmortem cerebellum and prefrontal cortex (PFC) from individuals with ASD as compared to neurotypical individuals. Using small RNA seq and the recently developed miRmedon tool for confident detection of miRNA editing, we compared editing levels between brain regions, individuals, and groups. We found nine editing sites significantly altered in autistic brains; 6 in PFC and 3 in the cerebellum. Target prediction of three differentially edited sites in PFC which located within the seed region followed by functional enrichment analysis imply on novel targets of edited miRNA which consequently lead to significant enrichment of ASD related pathways.

These results represent a first step in elucidating the potential role of miRNA editing in ASD, with ongoing analyses of the network-level impact of this editing on key pathways in neurodevelopment.