PRMT5 Maintains Homeostasis of the Intestinal Epithelium by Modulating Cell Proliferation and Survival
Abstract Intestinal homeostasis is sustained by self‐renewal of intestinal stem cells, which continuously divide and produce proliferative transit‐amplifying (TA) and progenitor cells. Protein arginine methyltransferases 5 (PRMT5) plays a crucial role in regulating homeostasis of various mammalian t...
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| Format: | Article |
| Language: | English |
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Wiley
2025-03-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202415559 |
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| author | Leilei Li Zhe Zhang Xu Wang Haiyong Zhao Liansheng Liu Yanhui Xiao Shan Hua Ye‐Guang Chen |
| author_facet | Leilei Li Zhe Zhang Xu Wang Haiyong Zhao Liansheng Liu Yanhui Xiao Shan Hua Ye‐Guang Chen |
| author_sort | Leilei Li |
| collection | DOAJ |
| description | Abstract Intestinal homeostasis is sustained by self‐renewal of intestinal stem cells, which continuously divide and produce proliferative transit‐amplifying (TA) and progenitor cells. Protein arginine methyltransferases 5 (PRMT5) plays a crucial role in regulating homeostasis of various mammalian tissues. However, its function in intestinal homeostasis remains elusive. In this study, conditional knockout of Prmt5 in the mouse intestinal epithelium leads to a reduction in stem cell population, suppression of cell proliferation, and increased cell apoptosis within the intestinal crypts, accompanied with shortened gut length, decreased mouse body weight, and eventual animal mortality. Additionally, Prmt5 deletion or its enzymatic inhibition in intestinal organoids in vitro also shows resembling cellular phenotypes. Methylome profiling identifies 90 potential Prmt5 substrates, which are involved in RNA‐related biological processes and cell division. Consistently, Prmt5 depletion in intestinal organoids leads to aberrant alternative splicing in a subset of genes related to the mitotic cell cycle. Furthermore, Prmt5 loss triggers p53‐mediated apoptosis in the intestinal epithelium. Collectively, the findings uncover an indispensable role of PRMT5 in promoting cell proliferation and survival, as well as maintaining stem cells in the gut epithelium. |
| format | Article |
| id | doaj-art-0d4ce47f8572484d9f9800e620c93ba1 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-0d4ce47f8572484d9f9800e620c93ba12025-08-20T03:44:23ZengWileyAdvanced Science2198-38442025-03-011212n/an/a10.1002/advs.202415559PRMT5 Maintains Homeostasis of the Intestinal Epithelium by Modulating Cell Proliferation and SurvivalLeilei Li0Zhe Zhang1Xu Wang2Haiyong Zhao3Liansheng Liu4Yanhui Xiao5Shan Hua6Ye‐Guang Chen7Guangzhou Laboratory Guangzhou 510700 ChinaGuangzhou Laboratory Guangzhou 510700 ChinaGuangzhou Laboratory Guangzhou 510700 ChinaGuangzhou Laboratory Guangzhou 510700 ChinaGuangzhou Laboratory Guangzhou 510700 ChinaGuangzhou Laboratory Guangzhou 510700 ChinaGuangzhou Laboratory Guangzhou 510700 ChinaGuangzhou Laboratory Guangzhou 510700 ChinaAbstract Intestinal homeostasis is sustained by self‐renewal of intestinal stem cells, which continuously divide and produce proliferative transit‐amplifying (TA) and progenitor cells. Protein arginine methyltransferases 5 (PRMT5) plays a crucial role in regulating homeostasis of various mammalian tissues. However, its function in intestinal homeostasis remains elusive. In this study, conditional knockout of Prmt5 in the mouse intestinal epithelium leads to a reduction in stem cell population, suppression of cell proliferation, and increased cell apoptosis within the intestinal crypts, accompanied with shortened gut length, decreased mouse body weight, and eventual animal mortality. Additionally, Prmt5 deletion or its enzymatic inhibition in intestinal organoids in vitro also shows resembling cellular phenotypes. Methylome profiling identifies 90 potential Prmt5 substrates, which are involved in RNA‐related biological processes and cell division. Consistently, Prmt5 depletion in intestinal organoids leads to aberrant alternative splicing in a subset of genes related to the mitotic cell cycle. Furthermore, Prmt5 loss triggers p53‐mediated apoptosis in the intestinal epithelium. Collectively, the findings uncover an indispensable role of PRMT5 in promoting cell proliferation and survival, as well as maintaining stem cells in the gut epithelium.https://doi.org/10.1002/advs.202415559cell proliferation and survivalintestinal homeostasisprotein arginine methylationprotein arginine methyltransferases 5stem cells |
| spellingShingle | Leilei Li Zhe Zhang Xu Wang Haiyong Zhao Liansheng Liu Yanhui Xiao Shan Hua Ye‐Guang Chen PRMT5 Maintains Homeostasis of the Intestinal Epithelium by Modulating Cell Proliferation and Survival Advanced Science cell proliferation and survival intestinal homeostasis protein arginine methylation protein arginine methyltransferases 5 stem cells |
| title | PRMT5 Maintains Homeostasis of the Intestinal Epithelium by Modulating Cell Proliferation and Survival |
| title_full | PRMT5 Maintains Homeostasis of the Intestinal Epithelium by Modulating Cell Proliferation and Survival |
| title_fullStr | PRMT5 Maintains Homeostasis of the Intestinal Epithelium by Modulating Cell Proliferation and Survival |
| title_full_unstemmed | PRMT5 Maintains Homeostasis of the Intestinal Epithelium by Modulating Cell Proliferation and Survival |
| title_short | PRMT5 Maintains Homeostasis of the Intestinal Epithelium by Modulating Cell Proliferation and Survival |
| title_sort | prmt5 maintains homeostasis of the intestinal epithelium by modulating cell proliferation and survival |
| topic | cell proliferation and survival intestinal homeostasis protein arginine methylation protein arginine methyltransferases 5 stem cells |
| url | https://doi.org/10.1002/advs.202415559 |
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