Spinal cord injury regulates circular RNA expression in axons

Frontiers in Molecular Neuroscience, 2023 · DOI: 10.3389/fnmol.2023.1183315 · Published: August 24, 2023

Simple Explanation

After spinal cord injury (SCI), axons, which do not spontaneously regenerate in the injured CNS, undergo changes in their RNA content, influencing neurorepair. This study identifies and characterizes axonal circular RNAs (circRNAs), a type of RNA molecule, and their role in axonal regeneration after SCI. The study found that spinal cord injury (SCI) alters the expression of certain genes, including circRNAs, in axons. One such circRNA, Rims2, can influence axonal regeneration. By manipulating an enzyme (ADAR1) that regulates circRNA formation, the researchers showed that increased circRNA levels promote axonal outgrowth of cortical neurons. Bioinformatic analysis suggests circRims2 can regulate the axonal translation of GAP-43, a protein that supports axonal elongation, via miRNAs. These axonal regulatory pathways will play a role in neurorepair.

Study Duration

Not specified

Participants

Female Sprague Dawley rats 3 months of age, two animals per condition; Primary rat and mouse cortical neuronal cultures

Evidence Level

Original Research

Key Findings

1
Axonal RNA is enriched using cold active proteases (CAP), which helps reduce artifacts during enzymatic digestion. Differentially expressed genes (DEGs), including circRNAs like Rims2, are detected after SCI.
2
Knockdown of ADAR1, the enzyme that regulates circRNA formation, promotes axonal outgrowth of cortical neurons and increases circRims2 levels.
3
CircRims2, via miRNAs, can regulate the axonal translation of GAP-43 to regulate axonal regeneration.

Research Summary

This study investigates the changes in axonal mRNA profiles, particularly circular RNAs (circRNAs), after spinal cord injury (SCI) to understand their role in axonal regeneration. The researchers developed a method to enrich axonal RNA and identified differentially expressed genes (DEGs) after SCI. The results show that SCI induces changes in DEGs, including circRNAs like Rims2. Ablation of ADAR1, an enzyme regulating circRNA formation, promotes axonal outgrowth, suggesting circRNAs' involvement in axonal regeneration. Bioinformatic analysis suggests a pathway where Rims2 regulates the axonal translation of GAP-43 via miRNAs, influencing axonal regeneration. This indicates that axonal regulatory pathways may play a role in neurorepair.

Practical Implications

Therapeutic Target Identification

The study identifies potential therapeutic targets, such as ADAR1 and circRims2, for promoting axonal regeneration after SCI.

RNA-Based Therapies

The findings suggest that RNA-based therapies, targeting axonal regulatory pathways, could play a role in neurorepair.

Understanding Axonal Regeneration

Elucidating the role of circRNAs in local axonal translation provides a better understanding of the multifaceted nature of axonal regeneration.

Study Limitations

1
The specific molecular mechanisms of circRims2 in modulating axonal outgrowth require further elucidation.
2
The study primarily focuses on circRims2; the roles of other identified circRNAs in axonal regeneration need further investigation.
3
Further analyses are required to have a better understanding the consequences of these changes in potentially dendritic and axonal signatures.

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