Year: 2025
Type: preprint
Abstract: Circular RNAs (circRNAs) arise from back-splicing of precursor RNAs and accumulate in the nervous system of animals, where they are thought to regulate gene expression and synaptic function. Here, we show that neuronal circRNA biosynthesis is mediated by the pan-neuronal RNA-binding protein ELAV. In Drosophila embryos, we characterize the circRNA landscape in normal and elav mutant neurons. We find that neuronal circRNAs are globally (>75%) depleted upon ELAV knockout, and induction of ELAV expression drives ectopic RNA circularization. In brain tissue, ELAV binds to pre-mRNA introns flanking putative circRNAs and decreases efficiency of linear splicing in favor of intron pairing at reverse complementary matches, inducing circularization. Together, our data demonstrate that ELAV directly modulates splicing decisions to generate the neuronal circRNA landscape.
Source: Genes & Development
Language: English
Topic: Circular RNAs in diseases
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
Awards: G1014860659, G1514386576, G259924242, G434337789, EXC 2189: CIBSS Centre for Integrative Biological Signalling Studies, G504090439, SFB 1381: Dynamische Organisation zellulärer Proteinmaschinerien: Von der Biogenese und modularen Assemblierung zur Funktion, Bloomington Drosophila Stock Center at Indiana University
OpenAlex ID: W4411142120