Zebrafish prmt5 arginine methyltransferase is essential for germ cell development

Abstract

Protein arginine methyltransferase 5 (Prmt5), a type II arginine methyltransferase, symmetrically dimethylates arginine in nuclear and cytoplasmic proteins. Prmt5 is involved in a variety of cellular processes including ribosome biogenesis, cellular differentiation, germ cell development, and tumorigenesis. However, the mechanisms by which prmt5 influences cellular processes have remained unclear. Here, prmt5 loss in zebrafish led to the expression of an infertile male phenotype due to a reduction in germ cell number, an increase in germ cell apoptosis, and the failure of gonads to differentiate into normal testes or ovaries. Moreover, arginine methylation of the germ-cell-specific proteins Zili and Vasa, as well as histones H3 (H3R8me2s) and H4 (H4R3me2s), was reduced in the gonads of prmt5-null zebrafish. This resulted in the downregulation of several Piwi pathway proteins, including Zili, and Vasa. In addition, various genes related to meiosis, gonad development, and sexual differentiation were dysregulated in the gonads of prmt5-null zebrafish. Our results revealed a novel mechanism associated with prmt5, i.e., prmt5 apparently controls germ cell development in vertebrates by catalyzing arginine methylation of the germline-specific proteins Zili and Vasa.