Regulation of DNA repair gene expression by PRMT5

Abstract

PRMT5 is a member of a class of enzymes called protein arginine methyltransferases (PRMTs) that play a role in maintaining genomic stability through post-translational modification of components of the TIP60 chromatin remodeling super complex. TIP60 is required primarily for chromatin remodeling at DNA double-strand breaks. Mutations in either TIP60 or PRMT5 affect repair by homologous recombination. A recent study has shown that in leukemia and lymphoma, PRMT5 also controls mRNA expression of TIP60 and other DNA repair genes by regulating alternative splicing. This analysis utilizes publicly available data from the Catalogue of Somatic Mutations in Cancer (COSMIC) to interrogate how PRMT5 expression correlates with expression levels of other key DNA repair genes: KAT5 (TIP60), H2A (H2AFX), TP53, TP53BP1, and RAD51 in all cancers. We find that indeed an increase in PRMT5 expression levels correlates with an increase in KAT5 levels. A weak correlation was also observed between PRMT5 and TP53, TP53BP1, and RAD51. These findings extend previous PRMT5 roles in controlling gene expression to all cancer types and further highlight the role of this enzyme not only in post-translational modification but also regulation of gene expression.

Figure 1. Correlation between PRMT5 expression and DNA repair gene expression in cancer samples

(A) The distribution of PRMT5 expression levels across different cancer types. Z-scores for TCGA samples for the indicated genes were separated into three categories: normal expression (green: Z-scores between -2 and +2), over-expressed (red: Z-scores over +2), and under-expressed (blue: Z-scores under -2). The Y-axis indicates counts of samples in each category. Please see text description for more details on interpretation of Z-scores. (B-F) Scatter plots showing the correlation between PRMT5 and the DNA repair genes KAT5 (TIP60), H2A (H2AFX), TP53, TP53BP1, and RAD51. PRMT5 expression is indicated on the x-axis, while the expression of the other repair genes is indicated on the y-axis. The data points represent individual samples, and the red line indicates the linear regression trend.