RNA Modifications Play Crucial Role in Neural Plasticity and Behavior

Researchers at the Zhongnan Hospital of Wuhan University have made significant findings regarding the role of RNA modifications in neural plasticity and behavior. The study reveals that pseudouridine (PS), a conserved RNA modification, fine-tunes transcript stability and splicing, and plays a critical role in neurodevelopment and behavioral adaptation. The research focuses on the infralimbic prefrontal cortex (ILPFC), a brain region essential for fear extinction memory, and identifies specific PS-dependent RNA processing mechanisms that regulate synaptic structural remodeling in this microcircuit.

Key Takeaways:

• The study highlights the significance of pseudouridine (PS) in neural plasticity and behavior, particularly in the infralimbic prefrontal cortex (ILPFC).
• PS-mediated epitranscriptomic regulation is essential for fine-tuning transcript stability and splicing, and is involved in neurodevelopment and behavior.
• The research demonstrates that PUS7, a pseudouridine synthase, is crucial for fear extinction memory formation and synaptic gene expression in the ILPFC.
• PUS7-dependent PS modification spatiotemporally regulates activity-dependent RNA dynamics in the ILPFC, providing evidence for the precise coordination of synaptic gene expression within behaviorally defined brain sub-regions.
• The study shows that knockdown of PUS7 in the ILPFC selectively impairs fear extinction memory formation without altering baseline fear expression, establishing a causal link between PS-dependent RNA processing and activity-dependent synaptic structural remodeling.
• The research bridges molecular RNA biology with systems neuroscience, revealing a novel mechanism for activity-dependent regulation of fear extinction in the ILPFC.

Statistics:

• The study focuses on the infralimbic prefrontal cortex (ILPFC), a brain region that requires precise synaptic remodeling for fear extinction memory formation.
• The research combines transcriptome-wide pseudouridylation profiling with behavioral analysis in mice, identifying selective PS enrichment at exons of synaptic regulatory genes within ILPFC during fear extinction learning.
• The study reveals that fear extinction in the ILPFC drives concomitant exonic PS deposition and upregulation of synaptogenic transcripts, processes that involve pseudouridine synthase PUS7.
• The research demonstrates that PUS7-mediated PS modification spatiotemporally regulates activity-dependent RNA dynamics in the ILPFC.

Sources:

• Molecular Brain. PUS7-dependent PS reshapes specific synaptic gene exons to facilitate fear extinction memory formation. Molecular Brain, 2025;18(1):80.
• BioMed Central. Molecular Brain. www.molecularbrain.com.
• Zhongnan Hospital of Wuhan University. Contact: Yuhan Dong, Dept. of Neurosurgery.