The Circle’s Journey: Mechanisms of CircRNA Trafficking in Neurons

Circular RNAs (circRNAs) have recently emerged as a class of abundant and remarkably stable non-coding RNAs preferentially enriched in the nervous system. In neurons, the fine-tuned spatial regulation of gene expression is critical for proper synaptic function; accordingly, several studies have demonstrated that circRNAs exhibit highly compartmentalized localization, specifically within dendrites, axons, and synapses. These spatial localization properties imply the presence of active transport mechanisms which control the intracellular trafficking of circRNAs. This review highlights current understanding of circRNA transport in neurons, focusing on molecular machinery driving synaptic enrichment. We specifically address the role of Ribonucleoprotein-based transport as a primary mechanism driving circRNA localization and examine how this spatial distribution influences synaptic plasticity and post-transcriptional gene regulation. Finally, we discuss the clinical implications of these processes, exploring the link between dysregulated RNA transport and the development of neuronal abnormalities.