Transition of CELF2 PAS usage promotes recovery of refractory JDM through alternative splicing regulation of CTSB.

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 fact

SUBMITTER: Wei J 

PROVIDER: S-EPMC12274826 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature