Neural circular RNAs are derived from synaptic genes and regulated by development and plasticity

Circular RNAs (circRNAs) have re-emerged as an interesting RNA species. Here, by deep RNA profiling in different mouse tissues, we observed that circRNAs are significantly enriched in brain.and a disproportionate fraction of them is derived from host genes that code for synaptic proteins. Moreover, based on separate profiling of the RNAs localized in neuronal cell bodies and neuropil, on average, circRNAs are more enriched in the neuropil than their host gene mRNA isoforms. Using high resolution in situ hybridization we, for the first time, visualized circRNA punctae in the dendrites of neurons. Consistent with the idea that circRNAs might regulate synaptic function, during development, many circRNAs change their abundance abruptly at a time corresponding to synaptogenesis. In addition, following a homeostatic downscaling of neuronal activity many circRNAs exhibit significant up or down-regulation. Together, our data indicate that brain circRNAs are positioned to respond to and regulate synaptic function.