Prmt5 deficient mouse B cells display RNA processing complexity and slower colorectal tumor progression

Protein arginine methyltransferase 5 (Prmt5) is essential for normal B‐cell development; however, the roles of Prmt5 in tumor‐infiltrating B cells in tumor therapy have not been well elucidated. Here, we revealed that CD19‐cre‐Prmt5fl/fl (Prmt5cko) mice showed smaller tumor weights and volumes in the colorectal cancer mouse model; B cells expressed higher levels of Ccl22 and Il12a, which attracted T cells to the tumor site. Furthermore, we used direct RNA sequencing to comprehensively profile RNA processes in Prmt5 deletion B cells to explore underline mechanisms. We found significantly differentially expressed isoforms, mRNA splicing, poly(A) tail lengths, and m6A modification changes between the Prmt5cko and control groups. Cd74 isoform expressions might be regulated by mRNA splicing; the expression of two novel Cd74 isoforms was decreased, while one isoform was elevated in the Prmt5cko group, but the Cd74 gene expression showed no changes. We observed Ccl22, Ighg1, and Il12a expression was significantly increased in the Prmt5cko group, whereas Jak3 and Stat5b expression was decreased. Ccl22 and Ighg1 expression might be associated with poly(A) tail length, Jak3, Stat5b, and Il12a expression might be modulated by m6A modification. Our study demonstrated that Prmt5 regulates B‐cell function through different mechanisms and supported the development of Prmt5‐targeted antitumor treatments. Prmt5 deletion B cells increase Ccl22 and Il12a production, showing slower tumor progression. Nanopore RNA sequence reveals that changes in mRNA alternative splicing, m6A modification, poly(A) tail length may be associated with transcripts expression and involved in B‐cell function. Results provide novel insights into the development of Prmt5‐targeted antitumor treatments.