Neuronal circular RNAs in a mouse model of autism spectrum disorders

Circular RNAs (circRNAs) represent a class of endogenous noncoding RNAs characterized by a covalently closed loop structure, resulting from a backsplicing reaction. Recent studies have shown their implication in post-transcriptional regulation of gene expression through several mechanisms as miRNA and protein binding, and mRNA trapping. circRNAs are highly enriched in the nervous system, as highlighted by RNAseq analyses in Drosophila and mammals. In the brain their expression is controlled during neuronal development and respond to synaptic activation, suggesting a role of circRNAs in the regulation of synaptic activity during development (Chen and Schuman, 2016). The Autism Spectrum Disorders (ASDs) are developmental disorders characterized by impairments in social interactions and communication, and by repetitive and stereotyped behaviors and interests. It has been hypothesized that the deregulation of the activity-dependent signaling network at the synapses could represent the key molecular component of this pathology (Ebert and Greenberg, 2013). In order to elucidate a possible role of circRNAs in autism, by next generation sequencing analyses of the circular transcriptome, we explored circRNA expression profile of the hippocampus of the BTBR T+tf/J (BTBR) mouse model for ASDs. Selected circRNAs candidates, differentially expressed in ASD, have been identified and further characterized. Region specific changes of circRNAs expression in BTBR mice and their regulation during differentiation and plasticity suggest their possible partecipation in neuronal signaling pathways altered in ASD. Our study suggests a possible role of circRNAs in the context of ASDs. Further analysis will allow us to better elucidate biological functions of BTBR altered circRNA, both in physiological and pathological conditions.