Neuronal activity-regulated alternative mRNA splicing

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Neuronal plasticity involves activity-regulated gene transcription, altering neuronal composition and structure.
• Gene expression changes are only part of the complexity; alternative splicing of messenger RNA (mRNA) also modulates transcriptional activity.
• Recent transcriptome-wide analyses reveal the extent of alternative splicing in activity-regulated genes.

Purpose of the Study:

• To summarize categories of alternative splicing contributing to synaptic remodeling.
• To provide an overview of activity-regulated alternatively spliced mRNAs impacting synaptic functions.
• To discuss regulatory determinants of alternative splicing, including splicing factors and epigenetic modifications.

Main Methods:

• Review of recent splicing-sensitive transcriptome-wide analyses.
• Analysis of studies detailing functional implications of differentially spliced mRNAs in synaptic proteins.
• Examination of research on splicing factors and epigenetic modifications in regulating alternative splicing.

Main Results:

• Alternative splicing generates diverse protein variants that can alter or block existing protein functions, contributing to synaptic reorganization.
• Differential exon usage leads to alternative proteins that impact pre- and postsynaptic terminal structure and function.
• Activity-induced alternative splicing affects untranslated regions (UTRs), influencing mRNA stability, translation, and subcellular targeting.

Conclusions:

• Alternative splicing is a key mechanism in activity-dependent neuronal plasticity and synaptic remodeling.
• Understanding alternative splicing of synaptic genes is critical for comprehending neuronal function and dysfunction.
• Splicing factors and epigenetic mechanisms are crucial regulators of activity-dependent alternative splicing in neurons.