PRMT5>regulates ovarian follicle development by facilitating Wt1 translation
- Institute of Zoology, Chinese Academy of Sciences, China
- Institute of Urology, Peking University Shenzhen Hospital, China
- Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, China
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.
Data availability
Our work did not generate any datasets or use any previously published datasets. Source data for Fig.4, 5, 6, 7 and figure supplement of Fig.1, Fig.5, Fig.6 have been provided.
Article and author information
Author details
Funding
Ministry of Science and Technology of the People's Republic of China (National key R&D program of China,2018YFC1004200)
- Min Chen
Ministry of Science and Technology of the People's Republic of China (National key R&D program of China,2018YFA0107700)
- Fei Gao
Chinese Academy of Sciences (Strategic Priority Research Program of the Chinese Academy of Sciences,XDB19000000)
- Fei Gao
National Natural Science Foundation of China (The National Science Fund for Distinguished Young Scholars,81525011)
- Fei Gao
National Natural Science Foundation of China (The National Natural Science Foundation of China,31970785,31601193,and 31671496))
- Fei Gao
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- T Rajendra Kumar, University of Colorado, United States
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of Institute of Zoology, Chinese Academy of Sciences (CAS). All animal experiments were carried out in accordance with the protocols approved by the Institutional Animal Care and Use Committee at the Institute of Zoology, Chinese Academy of Sciences (CAS) (Permit Number: SYXK 2018-0021).
Version history
- Received: March 30, 2021
- Preprint posted: April 7, 2021 (view preprint)
- Accepted: August 26, 2021
- Accepted Manuscript published: August 27, 2021 (version 1)
- Version of Record published: September 30, 2021 (version 2)
Copyright
© 2021, Chen et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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PRMT5>regulates ovarian follicle development by facilitating Wt1 translation
eLife 10:e68930.
https://doi.org/10.7554/eLife.68930
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