ArticleMolecular therapy. Nucleic acids2025
Transition of CELF2 PAS usage promotes recovery of refractory JDM through alternative splicing regulation of CTSB.
Article in Molecular therapy. Nucleic acids, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- RNA-Binding Proteins Regulate Cardiovascular Disease Progression Through Alternative Splicing and Alternative Polyadenylation.Journal of cardiovascular translational research · 2026Review
- Alternative polyadenylation and splicing regulation in refractory juvenile dermatomyositis: CELF2 at the crossroads.Molecular therapy. Nucleic acids · 2025Article
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Authors and funding
10 authors.
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Abstract
Alternative splicing (AS) and alternative polyadenylation (APA) are widespread in the immune system. However, their precise role in juvenile dermatomyositis (JDM) remains unclear. Based on the polyadenylation sequencing platform, we described APA landscape of refractory JDM before and after autologous hematopoietic stem cell transplantation (AHSCT) treatment and revealed a shortened APA event of RNA splicing genes in refractory JDM. Notably, the use of the proximal polyadenylation site (PAS) in CELF2 is a distinctive feature of refractory JDM, which transitions to the distal PAS following AHSCT. This shift in PAS utilization from proximal to distal affects CELF2 expression efficiency in both cells and JDM, contributing to resistance to drug therapy and activation of the tumor necrosis factor (TNF) signaling pathway. As a splicing regulator, the utilization of proximal PAS in CELF2 induces a series of AS events in immune genes, including a novel insertion of exons 2 and 3 in Cathepsin B (CTSB), which may act as a potential disruptive factor for refractory JDM treatment. This study emphasized the impact of post-transcript regulation in the pathology of refractory JDM, highlighting the importance of regulating CELF2 PAS usage in the treatment of refractory JDM. Therefore, targeting proximal PAS usage may serve as a potential clinical biomarker and therapeutic strategy for managing refractory JDM.
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