018 | Unveiling the function of a synaptically enriched circular RNA

Cellular and Molecular Neurobiology

Author: Giuliana Constanza Di Mauro | Email: giulidimauro@gmail.com

Giuliana Constanza Di Mauro , Camila Pannunzio , Sebastian Giusti , Antonia Marin-Burgin , Damian Refojo

1° Biomedicine Research Institute of Buenos Aires – CONICET – Partner Institute of the Max Planck Society

Circular RNAs (circRNAs) are a novel category of noncoding transcripts, originated from exonic regions and produced by backsplicing, process that generates a covalently linked single-stranded RNA molecule. Despite their recent discovery, circRNAs remain largely unexplored.
In a recent study, we performed a screening in which we identified numerous circRNAs in nerve tissue samples. Among these, we selected a transcript originating from the Dtnb (Dystrobrevin Beta) gene for in-depth functional analysis.
Expression levels in different mouse tissues revealed a pronounced enrichment of circDtnb in the brain, where this circular isoform of the transcripts outweighs the linear one. Further analysis in primary neuronal cultures revealed an increase in circDtnb expression during neuronal maturation, a distinct enrichment in neurons over astrocytes, and a preferential localization within synaptic compartments, with a greater circular-to-linear ratio.
Functional analysis of circDtnb involved loss-of-function experiments in primary neurons transfected with circDtnb-specific shRNA constructs. Downregulated cells showed a trend of increased mEPSP frequency in whole cell patch clamp recordings, and a consistent increase in dendritic spine count.
To study the role of circDtnb in vivo, we generated a novel loss-of-function transgenic mouse line. Our next objectives center on validating and characterizing this mouse model, aiming to provide valuable insights into circDtnb’s biological r