NeuroCirc: an integrative resource of circular RNA expression in the human brain.

MOTIVATION: CircRNAs are covalently closed RNA molecules that are particularly abundant in the brain. While circRNA expression data from the human brain is rapidly accumulating, integration of large-scale datasets remains challenging and time-consuming, and consequently an integrative view of circRNA expression in the human brain is currently lacking. RESULTS: NeuroCirc is a web-based resource that allows interactive exploration of multiple types of circRNA data from the human brain, including large-scale expression datasets, circQTL data and circRNA expression across neuronal differentiation and cellular maturation time-courses. NeuroCirc also allows users to upload their own circRNA expression data and explore it in the integrative platform, thereby supporting circRNA prioritization for experimental validation and functional studies. AVAILABILITY AND IMPLEMENTATION: NeuroCirc is freely available at: https://voineagulab.github.io/NeuroCirc/. The source code and user documentation are available at: https://github.com/Voineagulab/NeuroCirc. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Circular RNAs: The Brain Transcriptome Comes Full Circle.

Circular RNAs (circRNAs) are a class of RNA molecules with a covalently closed loop structure formed by back-splicing of exon-exon junctions. The detection of circRNAs across many eukaryotic species, often with cell-type- and tissue-type-specific expression, has catalyzed a growing interest in understanding circRNA biogenesis and their potential functions. circRNAs are enriched in the brain, and accumulate upon neuronal differentiation and depolarization, suggesting that these RNAs are an integral component of the brain transcriptome, and may play functional roles. Here, we give an overview of the current understanding of circRNA biogenesis and function, discuss how circRNAs contribute to transcriptome complexity in the brain, and discuss recent data on the functional roles of circRNAs in the brain. We also discuss emerging data on the role of circRNAs in brain disorders and address common challenges of circRNA quantification in postmortem human brain.

The Landscape of Circular RNA Expression in the Human Brain.

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).