The RNA‐Binding Protein PARN Remodeled 3′ UTR Structure Defines Poly(A)‐Loading Sites to Mediate Immunoglobulin Homeostasis

ABSTRACT Class Switch Recombination (CSR) is essential for generating high‐affinity antibody isotypes from IgM during adaptive humoral responses. Despite well‐established roles for various transcription factors, whether CSR is subject to dedicated post‐transcriptional control represents a significant gap in knowledge. By integrating conditional knockout models with SLE disease contexts, this study is the first to identify that the RNA‐binding protein, poly(A)‐specific ribonuclease (PARN), serves as a key positive regulator of antibody‐secreting cell function. Mechanistically, PARN preferentially binds 3′ UTRs and enhances the utilization of proximal poly(A) sites on a genome‐wide scale in vivo. Further results show that PARN binds UGUA and AA(U/A)AAA upstream elements to form a specific spatial RNA–protein complex, through which it exerts exonuclease activity to shorten poly(A) tails, thereby decreasing mRNA stability. In addition, we identified a class of functional genes—including Foxp1 —whose dynamic 3′ UTR changes directly regulate antibody secretion. This study reports a novel post‐transcriptional mechanism by which PARN promotes antibody production through modulation of 3′ UTR length. These findings not only advance our understanding of humoral immune regulation but also highlight a potential therapeutic target for autoimmune diseases such as SLE.