Circular RNA <i>circHomer1</i> mediates hippocampal functions via ribonucleoprotein granule transport and dendritic targeting of synaptic RNAs.

Abstract

Circular RNAs are backspliced, closed-loop RNAs previously believed to be noncoding by-products formed during transcription. Increasing evidence suggests that circular RNAs have crucial functions in the brain, such as regulating neuronal transmission and synaptic plasticity. However, the specific molecular mechanisms by which circular RNAs function remain largely unexplored. Here, we investigated how <i>circHomer1</i>, a brain-enriched circular RNA derived from the <i>Homer1</i> gene, affects hippocampus-dependent learning and memory. Our results demonstrate that <i>circHomer1</i> plays a vital role in mediating the dendritic targeting of messenger RNAs that encode postsynaptic proteins by acting as a molecular bridge between the motor protein Kinesin 1 and core components of neuronal ribonucleoprotein granules, including Fused in Sarcoma and Fragile X Mental Retardation Protein, at dendrites. This interaction influences synaptic function, the structural morphology of dendritic spines, and hippocampus-dependent spatial learning and memory. Thus, our study highlights a role of circular RNAs in mediating synaptic messenger RNA targeting to shape dendritic spines and consequently neuronal functions.