Spinal cord injury regulates circular RNA expression in axons

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Neurons transport mRNA to axons for local translation, crucial for neurorepair after spinal cord injury (SCI).
• The specific axonal mRNAs involved in neurorepair following SCI are not well understood.

Purpose of the Study:

• To identify axonal mRNAs involved in neurorepair after SCI.
• To understand the role of axonal RNAs in axonal regeneration.

Main Methods:

• Axonal mRNA-enriched preparations were obtained from control and SCI rat spinal cords using cold-active protease digestion.
• Differentially expressed genes (DEGs) were identified, mapped to biological processes, and validated using RT-qPCR and RNA-scope.
• Circular RNA (circRNA) identification and analysis were performed using bioinformatics tools and knockdown experiments.

Main Results:

• The study identified differentially expressed genes (DEGs) in axons after SCI, with axonogenesis being a significant pathway.
• Rims2, a circular RNA (circRNA), was identified in spinal cord axons, and its expression was altered after SCI.
• Inhibition of the RNA editing enzyme ADAR1, which affects circRNA formation, led to increased axonal outgrowth in primary cortical neurons.

Conclusions:

• SCI induces changes in axonal gene expression, including the presence of circRNAs like Rims2.
• Modulating circRNA formation, specifically by inhibiting ADAR1, promotes axonal regeneration.
• Axonal regulatory pathways involving circRNAs, miRNAs, and key proteins like GAP-43 are implicated in neurorepair after SCI.