Expression and function of circular RNAs in the mammalian brain

Mammalian brain presents extraordinary complexity reflected in the structure, function, and dynamic changes in the biological and physiological processes of development, maturity, and aging. Recent transcriptomic profiles from the brain tissues of distinct species have described a novel class of transcripts with a covalently closed-loop structure, called circular RNAs (circRNAs), which are produced by alternative back-splicing and derived from genes associated with synaptogenesis and neural activities. Brain is a tightly regulated and largely unexplored organ where circRNAs are highly enriched and expressed in the cell type-, spatiotemporal-specific, sex-biased, and age-related manner. Although the biological functions of most of the circRNAs in the brain remain elusive, increased evidence suggests that dynamic changes in circRNA expression are critical for brain function and the maintenance of physiological homeostasis in the brain. Here, we review the latest immense progresses in the understanding of circRNA expression and function in the mammalian brain. We also discuss possibly biological functions of circRNAs in the brain, which may provide new sights of understanding brain development and aging, as well as the pathogenesis of mental diseases.