PARN-Driven Alternative Polyadenylation Regulates Immunoglobulin Homeostasis in Antibody-Secreting Cells

Notably, systemic lupus erythematosus (SLE) frequently arises in the context of hypersensitivity; however, the precise mechanisms underlying its pathogenesis remain incompletely understood. Here, we demonstrate that poly(A)-specific ribonuclease (PARN), an RNA-binding protein, acts as a critical regulator of CSR.

In antibody-secreting cells, loss of PARN impairs CSR, resulting in a reduced proportion of cells producing post-switched immunoglobulin isotypes. Mechanistically, PARN specifically binds to the enhancer motif UGUA and the polyadenylation signal AAUAAA. PARN subsequently promotes transcript 3’ UTR shortening through alternative polyadenylation to regulate RNA stability.