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.