CRL2LRRC41-Mediated DDX5 Ubiquitination Enhances Interaction with ELAVL1 Preventing NOG mRNA Degradation and Sustaining Proliferation and Migration of Human Spermatogonial Stem Cell-Like Cell Line
Abstract Background Human spermatogonial stem cells (SSCs) exhibit a remarkable capacity for proliferation, crucial for sustaining spermatogenesis throughout life. While the Cullin-RING E3 ubiquitin ligase 2 (CRL2) complex is known to regulate various cellular functions, its precise role in human SS...
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2025-08-01
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| Online Access: | https://doi.org/10.1186/s12915-025-02363-z |
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| author | Bing Jiang Kehan Wang Haoyue Hu Wenxin Gao Cong Shen Xia Chen Xiaoyan Huang Jun Yu Yibo Wu Bo Zheng |
| author_facet | Bing Jiang Kehan Wang Haoyue Hu Wenxin Gao Cong Shen Xia Chen Xiaoyan Huang Jun Yu Yibo Wu Bo Zheng |
| author_sort | Bing Jiang |
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| description | Abstract Background Human spermatogonial stem cells (SSCs) exhibit a remarkable capacity for proliferation, crucial for sustaining spermatogenesis throughout life. While the Cullin-RING E3 ubiquitin ligase 2 (CRL2) complex is known to regulate various cellular functions, its precise role in human SSCs has not been fully elucidated. This study aimed to investigate a novel variant of the CRL2 complex, termed CRL2LRRC41, and its role in SSC function. Methods We utilized molecular biology techniques, including gene knockdown and functional assays, to assess the effects of CRL2LRRC41 on the proliferative and migratory abilities of human spermatogonial stem cell-like cell (SSCLC) line. Additionally, we employed proteomics and biochemical approaches to identify potential substrates of CRL2LRRC41. We specifically focused on ATP-dependent RNA helicase DDX5, a known regulator of spermatogenesis, to explore its interaction with CRL2LRRC41 and the downstream molecular mechanisms involved. Results Our findings revealed that the disruption or dysfunction of CRL2LRRC41 led to reduced proliferative and migratory abilities in human SSCLCs. Through our investigation, we identified DDX5 as a ubiquitination substrate of CRL2LRRC41. Notably, the ubiquitination of DDX5 fosters its interaction with the RNA-binding protein ELAVL1, without directing DDX5 towards degradation via the ubiquitin–proteasome system (UPS). This interaction enhances the stability of the downstream transcript, Noggin (NOG), thereby supporting human SSCLC proliferation and migration. Conclusions This study provides the first identification of the CRL2LRRC41 complex in human SSCLCs and elucidates the molecular mechanisms by which CRL2LRRC41 facilitates SSCLC function via ubiquitination-mediated protein interactions. These findings offer novel insights into the molecular underpinnings of male infertility. |
| format | Article |
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| institution | Kabale University |
| issn | 1741-7007 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
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| series | BMC Biology |
| spelling | doaj-art-83c3c2eedb174b4e8a39373d9be4fd0f2025-08-20T03:41:57ZengBMCBMC Biology1741-70072025-08-0123111910.1186/s12915-025-02363-zCRL2LRRC41-Mediated DDX5 Ubiquitination Enhances Interaction with ELAVL1 Preventing NOG mRNA Degradation and Sustaining Proliferation and Migration of Human Spermatogonial Stem Cell-Like Cell LineBing Jiang0Kehan Wang1Haoyue Hu2Wenxin Gao3Cong Shen4Xia Chen5Xiaoyan Huang6Jun Yu7Yibo Wu8Bo Zheng9Human Reproductive and Genetic Center, Affiliated Hospital of Jiangnan UniversityState Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproduction and Genetics, Gusu School, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Nanjing Medical UniversityHuman Reproductive and Genetic Center, Affiliated Hospital of Jiangnan UniversityState Key Laboratory of Reproductive Medicine and Offspring Health, Department of Histology and Embryology, School of Basic Medical Sciences, Nanjing Medical UniversityState Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproduction and Genetics, Gusu School, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Nanjing Medical UniversityCenter of Reproductive Medicine, Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong UniversityState Key Laboratory of Reproductive Medicine and Offspring Health, Department of Histology and Embryology, School of Basic Medical Sciences, Nanjing Medical UniversityInstitute of Reproductive Medicine, Medical School of Nantong University, Nantong UniversityHuman Reproductive and Genetic Center, Affiliated Hospital of Jiangnan UniversityState Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproduction and Genetics, Gusu School, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Nanjing Medical UniversityAbstract Background Human spermatogonial stem cells (SSCs) exhibit a remarkable capacity for proliferation, crucial for sustaining spermatogenesis throughout life. While the Cullin-RING E3 ubiquitin ligase 2 (CRL2) complex is known to regulate various cellular functions, its precise role in human SSCs has not been fully elucidated. This study aimed to investigate a novel variant of the CRL2 complex, termed CRL2LRRC41, and its role in SSC function. Methods We utilized molecular biology techniques, including gene knockdown and functional assays, to assess the effects of CRL2LRRC41 on the proliferative and migratory abilities of human spermatogonial stem cell-like cell (SSCLC) line. Additionally, we employed proteomics and biochemical approaches to identify potential substrates of CRL2LRRC41. We specifically focused on ATP-dependent RNA helicase DDX5, a known regulator of spermatogenesis, to explore its interaction with CRL2LRRC41 and the downstream molecular mechanisms involved. Results Our findings revealed that the disruption or dysfunction of CRL2LRRC41 led to reduced proliferative and migratory abilities in human SSCLCs. Through our investigation, we identified DDX5 as a ubiquitination substrate of CRL2LRRC41. Notably, the ubiquitination of DDX5 fosters its interaction with the RNA-binding protein ELAVL1, without directing DDX5 towards degradation via the ubiquitin–proteasome system (UPS). This interaction enhances the stability of the downstream transcript, Noggin (NOG), thereby supporting human SSCLC proliferation and migration. Conclusions This study provides the first identification of the CRL2LRRC41 complex in human SSCLCs and elucidates the molecular mechanisms by which CRL2LRRC41 facilitates SSCLC function via ubiquitination-mediated protein interactions. These findings offer novel insights into the molecular underpinnings of male infertility.https://doi.org/10.1186/s12915-025-02363-zLRRC41DDX5ELAVL1UbiquitinationSpermatogonial Stem Cells |
| spellingShingle | Bing Jiang Kehan Wang Haoyue Hu Wenxin Gao Cong Shen Xia Chen Xiaoyan Huang Jun Yu Yibo Wu Bo Zheng CRL2LRRC41-Mediated DDX5 Ubiquitination Enhances Interaction with ELAVL1 Preventing NOG mRNA Degradation and Sustaining Proliferation and Migration of Human Spermatogonial Stem Cell-Like Cell Line BMC Biology LRRC41 DDX5 ELAVL1 Ubiquitination Spermatogonial Stem Cells |
| title | CRL2LRRC41-Mediated DDX5 Ubiquitination Enhances Interaction with ELAVL1 Preventing NOG mRNA Degradation and Sustaining Proliferation and Migration of Human Spermatogonial Stem Cell-Like Cell Line |
| title_full | CRL2LRRC41-Mediated DDX5 Ubiquitination Enhances Interaction with ELAVL1 Preventing NOG mRNA Degradation and Sustaining Proliferation and Migration of Human Spermatogonial Stem Cell-Like Cell Line |
| title_fullStr | CRL2LRRC41-Mediated DDX5 Ubiquitination Enhances Interaction with ELAVL1 Preventing NOG mRNA Degradation and Sustaining Proliferation and Migration of Human Spermatogonial Stem Cell-Like Cell Line |
| title_full_unstemmed | CRL2LRRC41-Mediated DDX5 Ubiquitination Enhances Interaction with ELAVL1 Preventing NOG mRNA Degradation and Sustaining Proliferation and Migration of Human Spermatogonial Stem Cell-Like Cell Line |
| title_short | CRL2LRRC41-Mediated DDX5 Ubiquitination Enhances Interaction with ELAVL1 Preventing NOG mRNA Degradation and Sustaining Proliferation and Migration of Human Spermatogonial Stem Cell-Like Cell Line |
| title_sort | crl2lrrc41 mediated ddx5 ubiquitination enhances interaction with elavl1 preventing nog mrna degradation and sustaining proliferation and migration of human spermatogonial stem cell like cell line |
| topic | LRRC41 DDX5 ELAVL1 Ubiquitination Spermatogonial Stem Cells |
| url | https://doi.org/10.1186/s12915-025-02363-z |
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