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, roles of Prmt5 in tumor infiltrating B cells in tumor therapy have not been well elucidated. Here, we revealed that CD19-cre-Prmt5 fl/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 (DRS) to comprehensively profile RNA processes in Prmt5 deletion B cells to explore underline mechanisms. We found significantly differentially expressed isoforms (DEIs), 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 Prmt5cko group, but the Cd74 gene expression showed no changes. We observed Ccl22, Ighg1 and Il12a expression was significantly increased in Prmt5cko group, while 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. This article is protected by copyright. All rights reserved.