The history and function of a circular RNA

Cdr1as/ciRS-7 is a circular RNA conserved in mammals and highly expressed in brain. It features a large number of microRNA target sites bound in vivo by miR-7/miR-671. Cdr1as regulates synaptic activity under stress in a temporal, spatial, and neuron-specific manner. We review genetic, molecular, evolutionary, and physiological data to discuss how Cdr1as and its interactors form a functionally important network of non-coding RNAs that regulates neuronal adaptability. We provide a framework to explore potential roles of other non-coding RNA networks on brain function and their diagnostic and therapeutic potential. In this paper, the authors review how the circular RNA Cdr1as and its interacting non-coding RNAs regulate neuronal stress responses and synaptic activity, highlighting general principles of RNA-based regulatory mechanisms and their relevance for brain function, disease, and therapy.