PRMT5 regulates ovarian follicle development by facilitating Wt1 translation

Protein arginine methyltransferase 5 (Prmt5) is the major type II enzyme responsible for symmetric dimethylation of arginine. Here, we found that PRMT5 was expressed at high level in ovarian granulosa cells of growing follicles. Inactivation of Prmt5 in granulosa cells resulted in aberrant follicle...

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Autores principales:	Min Chen, Fangfang Dong, Zhiming Shen, Haowei Wu, Changhuo Cen, Xiuhong Cui, Shilai Bao, Fei Gao
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	PRMT5 ovary granulosa cells Wt1 IRES Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/1705f0a64b5a44d8b21a9ad6414811a0
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spelling	oai:doaj.org-article:1705f0a64b5a44d8b21a9ad6414811a02021-11-26T07:07:26ZPRMT5 regulates ovarian follicle development by facilitating Wt1 translation10.7554/eLife.689302050-084Xe68930https://doaj.org/article/1705f0a64b5a44d8b21a9ad6414811a02021-08-01T00:00:00Zhttps://elifesciences.org/articles/68930https://doaj.org/toc/2050-084XProtein arginine methyltransferase 5 (Prmt5) is the major type II enzyme responsible for symmetric dimethylation of arginine. Here, we found that 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 that 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.Min ChenFangfang DongMin ChenZhiming ShenHaowei WuChanghuo CenXiuhong CuiShilai BaoFei GaoeLife Sciences Publications LtdarticlePRMT5ovarygranulosa cellsWt1IRESMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	PRMT5 ovary granulosa cells Wt1 IRES Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	PRMT5 ovary granulosa cells Wt1 IRES Medicine R Science Q Biology (General) QH301-705.5 Min Chen Fangfang Dong Min Chen Zhiming Shen Haowei Wu Changhuo Cen Xiuhong Cui Shilai Bao Fei Gao PRMT5 regulates ovarian follicle development by facilitating Wt1 translation
description	Protein arginine methyltransferase 5 (Prmt5) is the major type II enzyme responsible for symmetric dimethylation of arginine. Here, we found that 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 that 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.
format	article
author	Min Chen Fangfang Dong Min Chen Zhiming Shen Haowei Wu Changhuo Cen Xiuhong Cui Shilai Bao Fei Gao
author_facet	Min Chen Fangfang Dong Min Chen Zhiming Shen Haowei Wu Changhuo Cen Xiuhong Cui Shilai Bao Fei Gao
author_sort	Min Chen
title	PRMT5 regulates ovarian follicle development by facilitating Wt1 translation
title_short	PRMT5 regulates ovarian follicle development by facilitating Wt1 translation
title_full	PRMT5 regulates ovarian follicle development by facilitating Wt1 translation
title_fullStr	PRMT5 regulates ovarian follicle development by facilitating Wt1 translation
title_full_unstemmed	PRMT5 regulates ovarian follicle development by facilitating Wt1 translation
title_sort	prmt5 regulates ovarian follicle development by facilitating wt1 translation
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/1705f0a64b5a44d8b21a9ad6414811a0
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PRMT5 regulates ovarian follicle development by facilitating Wt1 translation

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