PRMT5 & gt;regulates ovarian follicle development by facilitating < i > Wt1 < /i > translation

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 ofPrmt5 in granulosa cells resulted in aberrant follicle development and female infertility. InPrmt5-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 thatWt1 expression was regulated by PRMT5 at the protein level. PRMT5 facilitated IRES-dependent translation ofWt1 mRNA by methylating HnRNPA1. Moreover, the upregulation of steroidogenic genes inPrmt5-deficient granulosa cells was repressed byWt1overexpression. These results demonstrate PRMT5 participates in granulosa cell lineage maintenance by inducingWt1 expression. Our study uncovers a new role of post-translational arginine methylation in granulosa cell differentiation and follicle development.
Source: eLife - Category: Biomedical Science Tags: Cell Biology Developmental Biology Source Type: research