Limited Evidence of Microexon Skipping in Parkinson’s Disease and Spinocerebellar Ataxia Type 3

Methods

We performed a systematic analysis of microexon skipping in the frontal cortex of Parkinson’s disease (PD) patients and the cerebellum of Spinocerebellar Ataxia Type 3 (SCA3) patients using deep RNA-Sequencing of human postmortem brain tissue and corresponding SH-SY5Y cellular models. Microexon-associated junction usage was quantified based on splice junction reads derived from STAR alignments, followed by statistical testing and p-value calculation, with visualization using Sashimi plots.

Results: Across all datasets, 17 microexon-associated junction events showed statistically significant differential usage. Human brain tissue exhibited a substantially higher number of detectable microexons compared to cellular models, underscoring differences in splicing complexity between differentiated tissue and neuroblastoma-derived cells. While visual inspection suggested that effect sizes were generally small and variable across samples, the majority of microexon-containing genes were robustly expressed in both systems.

Conclusion: Our findings present an overview of microexon landscapes in PD and SCA3 and provide a systematic statistical analysis. Although large and consistent disease-specific skipping patterns were not observed under the present conditions, the data indicate that microexon regulation in neurodegeneration may involve subtle and context-dependent alterations that warrant further investigation in larger cohorts and more physiologically relevant cell models.