The Landscape of Circular RNA Expression in the Human Brain

Abstract

Background: Circular RNAs (circRNAs) are enriched in the mammalian brain and upregulated in response to neuronal differentiation and depolarization. These RNA molecules, formed by noncanonical back-splicing, have both regulatory and translational potential.

Methods: Here, we carried out an extensive characterization of circRNA expression in the human brain, in nearly 200 human brain samples, from both healthy controls and autism cases.

Results: We identified hundreds of novel circRNAs and demonstrated that circRNAs are not expressed stochastically, but rather as major isoforms. We characterized interindividual variability of circRNA expression in the human brain and showed that interindividual variability is less pronounced than variability between the cerebral cortex and cerebellum. Finally, we identified a circRNA coexpression module upregulated in autism samples, thereby adding another layer of complexity to the transcriptome changes observed in the autism brain.

Conclusions: These data provide a comprehensive catalog of circRNAs, as well as a deeper insight into their expression in the human brain, and are available as a free resource in browsable format (http://www.voineagulab.unsw.edu.au/circ_rna).

Keywords: Autism spectrum disorder; Circular RNA; Gene regulation; Human brain; Splicing; Transcriptome.