HnRNP A1 and A2B1 enforce Ezh2 mRNA splicing to promote germinal center B cell responses - PubMed
3 hours ago
- #Epigenetic regulation
- #RNA splicing
- #Germinal center B cells
- HnRNP A1 and A2B1 are essential for germinal center (GC) B cell responses in mice, as their loss impairs GC formation, B cell proliferation, and high-affinity antibody production.
- Mechanistically, hnRNP A1 and A2B1 bind to UAG-rich motifs in Ezh2 pre-mRNA to promote exon 14 inclusion, maintaining EZH2 catalytic activity; loss leads to exon skipping and production of an inactive EZH2 isoform (Ezh2Δ14).
- This inactive EZH2 results in reduced repression of Cdkn1a, causing CDKN1A accumulation that restricts B cell proliferation; deleting Cdkn1a partially rescues GC defects in hnRNP A1/A2B1-deficient B cells.
- The study reveals an hnRNP A1/A2B1-EZH2-CDKN1A axis linking RNA splicing to epigenetic regulation in B cell immunity.