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

Area of Science:

• Immunology
• Molecular Biology
• Oncology

Background:

• Protein arginine methyltransferase 5 (Prmt5) is crucial for B-cell development.
• The specific role of Prmt5 in tumor-infiltrating B cells and its therapeutic implications remain unclear.
• Understanding Prmt5's function in B cells is vital for developing novel cancer therapies.

Purpose of the Study:

• To investigate the role of Prmt5 in B cells within a colorectal cancer mouse model.
• To elucidate the molecular mechanisms by which Prmt5 influences B-cell function and tumor microenvironment.
• To explore the potential of Prmt5 as a therapeutic target for cancer treatment.

Main Methods:

• Utilized a CD19-cre-Prmt5^fl/fl (Prmt5cko) mouse model for colorectal cancer.
• Employed direct RNA sequencing to comprehensively analyze RNA processing in Prmt5-deficient B cells.
• Examined changes in gene expression, mRNA splicing, poly(A) tail lengths, and m6A modification.

Main Results:

• Prmt5 deletion in B cells led to smaller tumor weights and volumes.
• Prmt5cko B cells showed increased Ccl22 and Il12a expression, attracting T cells to the tumor.
• Significant alterations in isoform expression, mRNA splicing, poly(A) tail lengths, and m6A modification were observed in Prmt5cko B cells, affecting genes like Cd74, Ccl22, Ighg1, Il12a, Jak3, and Stat5b.

Conclusions:

• Prmt5 plays a significant role in regulating B-cell function and antitumor immunity.
• Prmt5 influences B-cell function through diverse mechanisms including RNA splicing, poly(A) tail regulation, and m6A modification.
• These findings support the development of Prmt5-targeted therapies for enhancing antitumor responses.