PRMT5 Regulates Ovarian Follicle Development by Facilitating Translation

Overview

Journal Elife

Specialty Biology

Date 2021 Aug 27

PMID 34448450

Citations 6

Authors

Fangfang Dong

Min Chen

Zhiming Shen

Haowei Wu

Changhuo Cen

Xiuhong Cui

Shilai Bao

Fei Gao

Affiliations

Soon will be listed here.

Abstract

Protein arginine methyltransferase 5 () 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 in granulosa cells resulted in aberrant follicle development and female infertility. In 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 expression was regulated by PRMT5 at the protein level. PRMT5 facilitated IRES-dependent translation of mRNA by methylating HnRNPA1. Moreover, the upregulation of steroidogenic genes in -deficient granulosa cells was repressed by overexpression. These results demonstrate that PRMT5 participates in granulosa cell lineage maintenance by inducing expression. Our study uncovers a new role of post-translational arginine methylation in granulosa cell differentiation and follicle development.

Citing Articles

Effects of Astaxanthin on the Physiological State of Porcine Ovarian Granulose Cells Cultured In Vitro.

Yang X, Zhou D, Gao L, Wang Y, Wang Y, Jia R Antioxidants (Basel). 2024; 13(10).

PMID: 39456440 PMC: 11504050. DOI: 10.3390/antiox13101185.

CLOCK inhibits the proliferation of porcine ovarian granulosa cells by targeting ASB9.

Huang L, Yuan H, Shi S, Song X, Zhang L, Zhou X J Anim Sci Biotechnol. 2023; 14(1):82.

PMID: 37280645 PMC: 10245596. DOI: 10.1186/s40104-023-00884-7.

Advances in Oocyte Maturation In Vivo and In Vitro in Mammals.

Jiang Y, He Y, Pan X, Wang P, Yuan X, Ma B Int J Mol Sci. 2023; 24(10).

PMID: 37240406 PMC: 10219173. DOI: 10.3390/ijms24109059.

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

Hou B, Mao M, Dong S, Deng M, Sun B, Guo Y Front Vet Sci. 2023; 10:1145594.

PMID: 37056233 PMC: 10086355. DOI: 10.3389/fvets.2023.1145594.

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

Chen M, Li S, Liu S, Zhang Y, Cui X, Lv L J Genet Genomics. 2022; 50(2):99-107.

PMID: 36494057 PMC: 9724560. DOI: 10.1016/j.jgg.2022.11.011.

References

Hsu S, Kubo M, Chun S, Haluska F, Housman D, Hsueh A . Wilms' tumor protein WT1 as an ovarian transcription factor: decreases in expression during follicle development and repression of inhibin-alpha gene promoter. Mol Endocrinol. 1995; 9(10):1356-66. DOI: 10.1210/mend.9.10.8544844. View

Rajpurohit R, Lee S, Park J, Paik W, Kim S . Enzymatic methylation of recombinant heterogeneous nuclear RNP protein A1. Dual substrate specificity for S-adenosylmethionine:histone-arginine N-methyltransferase. J Biol Chem. 1994; 269(2):1075-82. View

Di Lorenzo A, Bedford M . Histone arginine methylation. FEBS Lett. 2010; 585(13):2024-31. PMC: 3409563. DOI: 10.1016/j.febslet.2010.11.010. View

Cammas A, Pileur F, Bonnal S, Lewis S, Leveque N, Holcik M . Cytoplasmic relocalization of heterogeneous nuclear ribonucleoprotein A1 controls translation initiation of specific mRNAs. Mol Biol Cell. 2007; 18(12):5048-59. PMC: 2096577. DOI: 10.1091/mbc.e07-06-0603. View

Li Z, Yu J, Hosohama L, Nee K, Gkountela S, Chaudhari S . The Sm protein methyltransferase PRMT5 is not required for primordial germ cell specification in mice. EMBO J. 2014; 34(6):748-58. PMC: 4369312. DOI: 10.15252/embj.201489319. View

Smith P, Wilhelm D, Rodgers R . Development of mammalian ovary. J Endocrinol. 2014; 221(3):R145-61. DOI: 10.1530/JOE-14-0062. View

Richards J, Pangas S . New insights into ovarian function. Handb Exp Pharmacol. 2010; (198):3-27. PMC: 4551424. DOI: 10.1007/978-3-642-02062-9_1. View

Gao F, Zhang J, Wang X, Yang J, Chen D, Huff V . Wt1 functions in ovarian follicle development by regulating granulosa cell differentiation. Hum Mol Genet. 2013; 23(2):333-41. DOI: 10.1093/hmg/ddt423. View

Monniaux D . Driving folliculogenesis by the oocyte-somatic cell dialog: Lessons from genetic models. Theriogenology. 2016; 86(1):41-53. DOI: 10.1016/j.theriogenology.2016.04.017. View

10.

Chen M, Zhang L, Cui X, Lin X, Li Y, Wang Y . Wt1 directs the lineage specification of sertoli and granulosa cells by repressing Sf1 expression. Development. 2016; 144(1):44-53. DOI: 10.1242/dev.144105. View

11.

Stopa N, Krebs J, Shechter D . The PRMT5 arginine methyltransferase: many roles in development, cancer and beyond. Cell Mol Life Sci. 2015; 72(11):2041-59. PMC: 4430368. DOI: 10.1007/s00018-015-1847-9. View

12.

Gao F, Maiti S, Alam N, Zhang Z, Deng J, Behringer R . The Wilms tumor gene, Wt1, is required for Sox9 expression and maintenance of tubular architecture in the developing testis. Proc Natl Acad Sci U S A. 2006; 103(32):11987-92. PMC: 1567685. DOI: 10.1073/pnas.0600994103. View

13.

Bevilacqua E, Wang X, Majumder M, Gaccioli F, Yuan C, Wang C . eIF2alpha phosphorylation tips the balance to apoptosis during osmotic stress. J Biol Chem. 2010; 285(22):17098-111. PMC: 2878040. DOI: 10.1074/jbc.M110.109439. View

14.

Jo O, Martin J, Bernath A, Masri J, Lichtenstein A, Gera J . Heterogeneous nuclear ribonucleoprotein A1 regulates cyclin D1 and c-myc internal ribosome entry site function through Akt signaling. J Biol Chem. 2008; 283(34):23274-87. PMC: 2516998. DOI: 10.1074/jbc.M801185200. View

15.

Ikeda Y, Lala D, Luo X, Kim E, Moisan M, Parker K . Characterization of the mouse FTZ-F1 gene, which encodes a key regulator of steroid hydroxylase gene expression. Mol Endocrinol. 1993; 7(7):852-60. DOI: 10.1210/mend.7.7.8413309. View

16.

Coldwell M, Mitchell S, Stoneley M, MacFarlane M, Willis A . Initiation of Apaf-1 translation by internal ribosome entry. Oncogene. 2000; 19(7):899-905. DOI: 10.1038/sj.onc.1203407. View

17.

Roy R, Huang Y, Seckl M, Pardo O . Emerging roles of hnRNPA1 in modulating malignant transformation. Wiley Interdiscip Rev RNA. 2017; 8(6). DOI: 10.1002/wrna.1431. View

18.

Baird S, Turcotte M, Korneluk R, Holcik M . Searching for IRES. RNA. 2006; 12(10):1755-85. PMC: 1581980. DOI: 10.1261/rna.157806. View

19.

Stocco C . Aromatase expression in the ovary: hormonal and molecular regulation. Steroids. 2008; 73(5):473-87. PMC: 2365984. DOI: 10.1016/j.steroids.2008.01.017. View

20.

Stoneley M, Willis A . Cellular internal ribosome entry segments: structures, trans-acting factors and regulation of gene expression. Oncogene. 2004; 23(18):3200-7. DOI: 10.1038/sj.onc.1207551. View