SFRS8 Regulates Memory by Modulating RNA Splicing of Synaptic Genes

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Serine and arginine-rich (SR) proteins are vital splicing factors.
• SFRS8 is abundant in the brain, but its specific functions are unknown.
• Synaptic plasticity and memory depend on precise gene expression regulation.

Purpose of the Study:

• To elucidate the role of SFRS8 in the brain.
• To investigate the molecular mechanisms underlying SFRS8 function.
• To determine the impact of SFRS8 on synaptic integrity and memory.

Main Methods:

• Investigated SFRS8 interaction with SF3B3, a U2 snRNP component.
• Analyzed SFRS8's regulation of Psd95 pre-mRNA splicing.
• Utilized in vivo (hippocampal knockdown) and in vitro (cultured neurons) models.

Main Results:

• SFRS8 directly binds SF3B3 to control alternative splicing of synaptic genes.
• SFRS8 regulates exon 18 skipping in Psd95, affecting PSD95 protein levels.
• SFRS8 knockdown reduced synaptic protein levels, dendritic spine density, and impaired memory in mice.

Conclusions:

• SFRS8 is essential for maintaining synaptic protein homeostasis and density.
• SFRS8 modulates memory function through alternative splicing of synaptic genes.
• SFRS8's interaction with SF3B3 is key to its role in synaptic regulation.