Neural circular RNAs are derived from synaptic genes and regulated by development and plasticity

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Circular RNAs (circRNAs) are a class of RNA molecules with a unique covalently closed loop structure.
• Recent studies highlight their potential roles in various biological processes, including neuronal function.

Purpose of the Study:

• To investigate the prevalence and localization of circRNAs in the mouse brain.
• To explore the relationship between circRNAs and synaptic function, development, and neuronal activity.

Main Methods:

• Deep RNA profiling across different mouse tissues.
• Fractionation of RNAs from neuronal cell bodies and neuropil.
• High-resolution in situ hybridization for visualizing circRNA localization.
• Analysis of circRNA abundance changes during synaptogenesis and in response to altered neuronal activity.

Main Results:

• CircRNAs are highly enriched in the brain, with a significant portion originating from genes encoding synaptic proteins.
• CircRNAs are more concentrated in the neuropil than their corresponding mRNA isoforms.
• CircRNAs are detected as punctae within neuronal dendrites.
• CircRNA abundance significantly changes during synaptogenesis and in response to homeostatic regulation of neuronal activity.

Conclusions:

• Brain circRNAs are strategically located to influence synaptic function.
• CircRNAs play a role in neuronal development and plasticity.
• These findings position circRNAs as key regulators of synaptic activity and function.