circular RNA function in post-mitotic neurons

Circular RNAs (circRNAs) are a large class of highly stable, primarily non-coding RNAs characterized by their covalently closed ends. Despite their prominent abundance in the brain, the function of circRNAs in neurons is still widely elusive. Notably, there is emerging evidence that circRNAs might bind microRNAs (miRNAs) as well as RNA-binding proteins (RBPs) and could thus represent a means to regulate local protein synthesis in neurons. To test this hypothesis, we use an integrative approach, combining bioinformatic analysis with a broad range of cell biological and biochemical assays in rat primary neurons, such as RNAseq, RNAi-based knockdown, qRT-PCR, single-molecule FISH, Northern blot etc. Through this approach, we hope to identify dendritic circRNAs with a crucial function in synapse development. Moreover, the findings from our in vitro study in primary neurons will lay a framework for comprehensive follow-up studies addressing the function of circRNAs in the intact brain. Taken together, our project promises to uncover a new facet of non-coding RNA regulation in synaptogenesis, thereby expanding our understanding of the sophisticated mechanisms underlying neural circuit development and neurodevelopmental disorders characterized by synaptic dysfunction (e.g. autism-spectrum disorders).