Prmt5: a guardian of the germline protects future generations

Abstract

Primordial germ cells (PGCs) are the embryonic precursors of the germ cell lineage that form sperm and egg cells. It is of great importance to preserve the germline from DNA damage and potentially from epimutations in order to ensure the survival of future generations. Recent research highlights the role of the protein arginine methyltransferase 5 (PRMT5) as an important player in DNA protection during germline development in the mouse (Kim et al, & Li et al, 2015).

Figure 1

Conditional deletion of Prmt5 in the mouse germline reveals the arginine methyltransferase as a guardian of germline integrity PRMT5 is required for survival and proliferation of primordial germ cells (pink) that is compromised between E10.5 and E13.5 in Prmt5 KO PGCs. PRMT5 is dynamically expressed during mouse germline development. Prmt5 conditional KO in the germline leads to reduced H2A/H4R3 methylation that induces activation of TEs and may subsequently lead to DNA damage. Additionally, lack of methylation of spliceosomal proteins leads to differential splicing events, which in turn control DNA damage response activation. This DNA damage may lead to apoptosis of PGCs with TE activity in order to protect the germline for future generations. Model based on Kim et al (2014) and Li et al (2015).