Computational Splicing Analysis of Transcriptomic Data Reveals Sulforaphane Modulation of Alternative mRNA Splicing of DNA Repair Genes in Differentiated SH-SY5Y Neurons

Sulforaphane (SFN) is a bioactive compound belonging to the isothiocyanate family, known for its neuroprotective properties. While transcriptomic studies have highlighted SFN's role in regulating gene expression, its impact on alternative splicing (AS), a key regulatory mechanism in neuronal metabolism, remains underexplored. In this study, we investigated whether SFN pre-treatment influences mRNA splicing patterns in an in vitro neuronal model using retinoic acid (RA)-differentiated SH-SY5Y cells. Using a dedicated RNA-seq-based splicing analysis pipeline, we identified 194 differential alternative splicing events (DASEs) associated with SFN treatment. Gene Ontology enrichment revealed significant over-representation of DNA repair processes. To better understand the functional implications, we integrated in silico predictions of premature stop codons, DASE/miRNA hybridizations, and DASE/RNA-binding protein (RBP) motif occurrences. Our findings suggest that SFN may modulate splicing of key DNA repair genes, contributing to protecting neurons against DNA damage. These preliminary results underscore a novel layer of SFN's molecular effects and propose it as a valuable adjuvant in physiological conditions to enhance cellular health. Further studies are warranted to dissect the mechanistic underpinnings of SFN-mediated AS and its relevance in DNA-damage-related disorders.