PRMT5 regulates ovarian follicle development by facilitating Wt1 translation

Abstract

Protein arginine methyltransferase 5 (Prmt5) is the major type II enzyme responsible for symmetric dimethylation of arginine. Here, we found PRMT5 was expressed at high level in ovarian granulosa cells of growing follicles. Inactivation of Prmt5 in granulosa cells resulted in aberrant follicle development and female infertility. In Prmt5-knockout mice, follicle development was arrested with disorganized granulosa cells in which WT1 expression was dramatically reduced and the expression of steroidogenesis-related genes was significantly increased. The premature differentiated granulosa cells were detached from oocytes and follicle structure was disrupted. Mechanism studies revealed that Wt1 expression was regulated by PRMT5 at the protein level. PRMT5 facilitated IRES-dependent translation of Wt1 mRNA by methylating HnRNPA1. Moreover, the upregulation of steroidogenic genes in Prmt5-deficient granulosa cells was repressed by Wt1 overexpression. These results demonstrate PRMT5 participates in granulosa cell lineage maintenance by inducing Wt1 expression. Our study uncovers a new role of post-translational arginine methylation in granulosa cell differentiation and follicle development.

Transcriptome analysis reveals mRNAs and long non-coding RNAs associated with fecundity in the hypothalamus of high-and low-fecundity goat

“…In addition, DE lncRNA ENSCHIT00000009862 and ENSCHIT00000009864 in the hypothalamus are predicted act on the target gene FEZF1, a family of Fez transcription factors that control neurogenesis and cellular fate in the developing mammalian nervous system (43). Zinc finger transcription factor FEZF1 is a highly conserved family of transcription factors that play a role in neurogenesis, developmental patterns, cell fate regulation and axonal guidance (44). And the function of the down-regulated target gene FEZF1 is consistent with the corresponding regulation of neurogenesis (GO:0050767) GO term in our sequencing results.…”

“…In addition, we also found that the target gene WT1 corresponding to up-regulated DE lncRNA ENSCHIT00000002459 and ENSCHIT00000002460 was also closely related to ovarian follicular development in female animals. WT1 is a nuclear transcription factor, and Chen et al ( 45 ) found that protein arginine methyltransferase 5 (PRMT5) deficient mouse follicular granulosa cells expressing steroid genes were reversed by WT1 overexpression, indicating that PRMT5 is necessary to prevent premature differentiation of granulosa cells by regulating WT1 expression. There is also a down-regulated DElncRNAENSCHIT00000003170 predicted target gene MMP9, as a matrix metalloproteinase regulated by LH or progesterone, which not only affects cell growth, differentiation, proliferation and apoptosis, but also plays an important role in ovulation and gonadal formation in female animals ( 46 ).…”

Infection of SARS-CoV-2 causes severe pathological changes in mouse testis

“…Immunohistochemistry and immunofluorescence analysis were performed as described previously ( Chen et al, 2021 ). After rehydration and antigen retrieval, the 5-μm sections were blocked with 5% BSA, incubated with the primary antibody for 1 hr and the corresponding secondary antibody for 1 hr.…”

Generation of Pmel‐dependent conditional and inducible Cre‐driver mouse line for melanocytic‐targeted gene manipulation

“…During the characterization of the Pmel P2A-TetON3G-TRE3G-iCre mouse line, we realized that this line is also useful for clearly identifying the PMEL-expressing cells. Therefore, we further characterized the Immunohistological analysis revealed that tdTomato expression in these organs is restricted to specific cell types, including mesothelial cells (WT1-positive) of the heart and lung (Figure 7ad) (Rui et al, 2014), granulosa cells (WT1-positive) of the ovary (Figure 7e,f) (Chen et al, 2021), luminal epithelial cells (NKX3.1positive) of the anterior prostate (Figure 7g,h) (Kim et al, 2002), parietal cells (ATP4B-positive) of the muscular stomach (Figure 7i,j) (Spicer et al, 2000), and Sertoli cells (WT1-positive) and Leydig cells (CYP17A1-positive) of the testis (Figure 7k-m) (Penny et al, 2017;Wang et al, 2013). To examine whether these tdTomato-positive cells express PMEL protein, we performed immunofluorescent staining using a specific antibody against PMEL protein.…”