An EJC-independent novel isoform of MAGOH: the MAGOH-Δ37 isoform and its interactome capture.

The Exon-Junction Complex (EJC) is essential for post-transcriptional gene regulation, with MAGOH as one of its core components, known for its involvement in mRNA surveillance and translation. In this study, we characterize an evolutionarily conserved, alternatively spliced isoform of MAGOH, i.e. MAGOH-Δ37, which has remained largely unexplored until now. Our study reveals that, unlike canonical MAGOH, MAGOH-Δ37 does not interact with known EJC proteins such as EIF4A3, RBM8A, RNPS1, or SAP18, suggesting a distinct functional role independent of the EJC. Intriguingly, both MAGOH and MAGOH-Δ37 associate with proteins implicated in neurodegenerative disorders, suggesting EJC-independent interactions. Furthermore, MAGOH and its isoform MAGOH-Δ37 interact with ubiquitin and were found to be upregulated upon proteasomal inhibition. The association of the isoforms with a distinct polyubiquitin signature suggests a potential role in the ubiquitin-proteasome system, either as targets or binding partners. These findings provide new insights into the roles of MAGOH isoforms in stress-related pathways, with implications for their involvement in neurodegenerative conditions.