Adv Sci (Weinh). 2026 May 12:e75609. doi: 10.1002/advs.75609. Online ahead of print.
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.
PMID:42118147 | DOI:10.1002/advs.75609