Recently, Associate Researcher Bo Zheng from the Gusu School, Nanjing Medical University (NMU) published a research paper titled “RNF187 Facilitates Proliferation and Migration of Human Spermatogonial Stem Cells Through WDR77 Polyubiquitination” in the journal Cell Proliferation. The study reveals the critical mechanism by which protein ubiquitination regulates the fate determination of human spermatogonial stem cells, providing new insights into the etiology of male infertility.
The study revealed that the expression level of the E3 ubiquitin ligase RNF187 is positively correlated with the proliferative and migratory capacity of human spermatogonial stem cells (SSCs). Through co-immunoprecipitation (Co-IP) and mass spectrometry analysis, WDR77 was identified as an interacting protein of RNF187.
Mechanistically, RNF187 recognises the K118 site of WDR77 through lysine 48-linked polyubiquitination, subsequently mediating its degradation via the ubiquitin-proteasome system (UPS). Further studies have revealed that decreased expression of WDR77 diminishes the symmetric dimethylation at H4R3 (H4R3me2s), a modification catalysed by its interacting protein, the arginine methyltransferase PRMT5. This reduction lifts the transcriptional repression of early growth response protein 1 (EGR1), a positive regulator for human SSC maintenance.
This study elucidates the critical role of the RNF187/WDR77/PRMT5/EGR1 signaling axis in regulating the proliferation and migration of human SSCs, offering a novel therapeutic strategy for treating non-obstructive azoospermia (NOA) caused by SSC dysfunction.
Bo Zheng, Associate Researcher at the Gusu School of NMU, Yibo Wu, Researcher at Jiangnan University, Tingting Gao, Assistant Researcher from Changzhou Maternal and Child Health Care Hospital, and Jun Yu, Professor from the Institute of Reproductive Medicine, Medical School of Nantong University, are the co- corresponding authors of this paper. Haoyue Hu and Bing Jiang, graduate students at Jiangnan University, and Xiaoxue Xi, Associate Chief Physician at Gusu School are the co-first authors of this paper. This research was supported by the National Natural Science Foundation of China and the Natural Science Foundation of Jiangsu Province.
Link to the original paper:https://doi.org/10.1111/cpr.70042
(Drafted by the Department of Science and Technology, the Affiliated Suzhou Hospital of NMU; Reviewed by Changjun Wang; Translation reviesed by Zhang Bei)
