Protein Arginine Methyltransferase 1 Is Essential for the Meiosis of Male Germ Cells

Abstract

Protein arginine methyltransferase 1 (PRMT1) is a major enzyme responsible for the formation of methylarginine in mammalian cells; however, its function in vivo is not well understood due to its early embryonic lethality in null mice exhibiting spontaneous DNA damage, cell cycle delays, and defects in check point activation. Here, we generated germ cell-specific Prmt1 knock-out (KO) mice to evaluate the function of PRMT1 in spermatogenesis. Our findings demonstrate that PRMT1 is vital for male fertility in mice. Spermatogenesis in Prmt1 KO mice was arrested at the zygotene-like stage of the first meiotic division due to an elevated number of DNA double-strand breaks (DSBs). There was a loss of methylation in meiotic recombination 11 (MRE11), the key endonuclease in MRE11/RAD50/NBS 1 (MRN) complex, resulting in the accumulation of SPO11 protein in DSBs. The ATM-mediated negative feedback control over SPO11 was lost and, consequently, the repair pathway of DSBs was highly affected in PRMT1 deficient male germ cells. Our findings provide a novel insight into the role of PRMT1-mediated asymmetric demethylation in mouse spermatogenesis.

PRMT1 in human neoplasm: cancer biology and potential therapeutic target

“…Furthermore, PRMT1-mediated histone H4R3me2a methylation is crucial for regulating cell proliferation in various organs and serves as a key regulator of normal vertebrate development and growth [ 22 ]. Studies have demonstrated PRMT1’s involvement in regulating the self-renewal of hematopoietic stem cells and normal hematopoiesis [ 23 ], as well as in the normal development of lymphocytes [ 24 , 25 ], the differentiation and proliferation of intestinal cells [ 26 ], myelin regeneration [ 27 ], and spermatogenesis [ 28 ]. Notably, the absence of PRMT1 in mice results in a significant decrease in the proliferation of palate mesenchymal cells, ultimately preventing the palatal shelves from reaching the midline and resulting in a complete cleft palate phenotype [ 29 ].…”