neuronal circRNA expression after spliceosome inhibition

Circular RNAs (circRNAs) are an important class of regulatory RNAs and have been shown to be the most prevalent in the brain compared to other tissue. To understand the processes governing neuronal circRNA biogenesis, we pharmacologically inhibited the spliceosome in primary rat hippocampal neurons and profiled circRNAs using RNA-sequencing. We identified 776 robustly expressed circRNAs in control and treatment condition. Among them, we observed over 100 circRNAs that were up-regulated and a few that were down-regulated after spliceosome inhibition. Bioinformatic analysis revealed that up-regulated circRNAs possess significantly longer flanking introns that harbor a higher number of distinct repeat sequences and reverse complementary motifs compared to un-changed circRNAs. Taken together, our data demonstrate that the biogenesis of circRNAs containing distinct intronic features becomes favored under conditions of limited spliceosome activity.