PATL2 mutations affect human oocyte maternal mRNA homeostasis and protein interactions in cell cycle regulation
Abstract Background Oocyte maturation defect (OMD) and early embryonic arrest result in female infertility. Previous studies have linked biallelic mutations in the PATL2 gene to OMD, yet the underlying mechanism remains largely unknown. Results This study uncovers three novel mutations (c.1201G >...
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BMC
2024-12-01
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| Series: | Cell & Bioscience |
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| Online Access: | https://doi.org/10.1186/s13578-024-01341-2 |
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| author | Yin-Li Zhang Zhanhong Hu Huifang Jiang Jiamin Jin Yan Zhou Mengru Lai Peipei Ren Siya Liu Ying-Yi Zhang Yan Rong Wei Zheng Shen Zhang Xiaomei Tong Songying Zhang |
| author_facet | Yin-Li Zhang Zhanhong Hu Huifang Jiang Jiamin Jin Yan Zhou Mengru Lai Peipei Ren Siya Liu Ying-Yi Zhang Yan Rong Wei Zheng Shen Zhang Xiaomei Tong Songying Zhang |
| author_sort | Yin-Li Zhang |
| collection | DOAJ |
| description | Abstract Background Oocyte maturation defect (OMD) and early embryonic arrest result in female infertility. Previous studies have linked biallelic mutations in the PATL2 gene to OMD, yet the underlying mechanism remains largely unknown. Results This study uncovers three novel mutations (c.1201G > T, c.1284delA and c.1613 + 2_1613 + 3insGT) and three reported mutations (c.1204 C > T, c.1271T > C, c.223 − 14_223-2delCCCTCCTGTTCCA) in the PATL2 gene across five unrelated individuals exhibiting OMD, oocyte death, and early embryonic arrest. RNA sequencing revealed that PATL2 mutations decreased mRNA storage in human germinal vesicle (GV) oocytes and impeded mRNA decay during maturation and in early embryos. We demonstrate that PATL2 interacts with CPEB1 and TUT7 in human oocytes to maintain mRNA homeostasis. Additionally, we observed a reduction in CCNB1 and CCNE1 mRNA levels in PATL2-mutant GV oocytes, which may be linked to GV arrest. Employing both wild-type and mutated PATL2V401F/R402W variants, we characterized the protein interactome of PATL2, identifying disruptions of PATL2V401F/R402W variants predominantly affecting cell cycle-related proteins, including CDC23, APC1 and MAD2L1. PATL2’s interaction with and stabilization of CDC23 in oocytes may elucidate the mechanisms behind the mutation-induced MI arrest. PALT2 is required for the efficient mRNA translation and it maintains the protein level of CDC23, APC1 and MAD2L1 in mouse GV oocyte. Conclusion PATL2 plays a critical role in regulating mRNA accumulation and decay in human oocytes, potentially through interactions with CPEB1 and TUT7, respectively. Mutations in PATL2 lead to oocyte meiosis defects by affecting the mRNA accumulation, mRNA translation, and direct binding to and stabilizing proteins related to cell cycle regulation, such as CCNB1 and CDC23. This study expands the mutational spectrum of PATL2 and provides new insights into the molecular mechanisms underlying PATL2 mutation-associated oocyte maturation disorders. |
| format | Article |
| id | doaj-art-eee8c35daf164d6ebddc6a832f6012e5 |
| institution | Kabale University |
| issn | 2045-3701 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
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| series | Cell & Bioscience |
| spelling | doaj-art-eee8c35daf164d6ebddc6a832f6012e52025-01-05T12:47:52ZengBMCCell & Bioscience2045-37012024-12-0114112210.1186/s13578-024-01341-2PATL2 mutations affect human oocyte maternal mRNA homeostasis and protein interactions in cell cycle regulationYin-Li Zhang0Zhanhong Hu1Huifang Jiang2Jiamin Jin3Yan Zhou4Mengru Lai5Peipei Ren6Siya Liu7Ying-Yi Zhang8Yan Rong9Wei Zheng10Shen Zhang11Xiaomei Tong12Songying Zhang13Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityAssisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityAssisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityAssisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityAssisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityAssisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityAssisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityAssisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityAssisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityAssisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityClinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XiangyaClinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XiangyaAssisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityAssisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityAbstract Background Oocyte maturation defect (OMD) and early embryonic arrest result in female infertility. Previous studies have linked biallelic mutations in the PATL2 gene to OMD, yet the underlying mechanism remains largely unknown. Results This study uncovers three novel mutations (c.1201G > T, c.1284delA and c.1613 + 2_1613 + 3insGT) and three reported mutations (c.1204 C > T, c.1271T > C, c.223 − 14_223-2delCCCTCCTGTTCCA) in the PATL2 gene across five unrelated individuals exhibiting OMD, oocyte death, and early embryonic arrest. RNA sequencing revealed that PATL2 mutations decreased mRNA storage in human germinal vesicle (GV) oocytes and impeded mRNA decay during maturation and in early embryos. We demonstrate that PATL2 interacts with CPEB1 and TUT7 in human oocytes to maintain mRNA homeostasis. Additionally, we observed a reduction in CCNB1 and CCNE1 mRNA levels in PATL2-mutant GV oocytes, which may be linked to GV arrest. Employing both wild-type and mutated PATL2V401F/R402W variants, we characterized the protein interactome of PATL2, identifying disruptions of PATL2V401F/R402W variants predominantly affecting cell cycle-related proteins, including CDC23, APC1 and MAD2L1. PATL2’s interaction with and stabilization of CDC23 in oocytes may elucidate the mechanisms behind the mutation-induced MI arrest. PALT2 is required for the efficient mRNA translation and it maintains the protein level of CDC23, APC1 and MAD2L1 in mouse GV oocyte. Conclusion PATL2 plays a critical role in regulating mRNA accumulation and decay in human oocytes, potentially through interactions with CPEB1 and TUT7, respectively. Mutations in PATL2 lead to oocyte meiosis defects by affecting the mRNA accumulation, mRNA translation, and direct binding to and stabilizing proteins related to cell cycle regulation, such as CCNB1 and CDC23. This study expands the mutational spectrum of PATL2 and provides new insights into the molecular mechanisms underlying PATL2 mutation-associated oocyte maturation disorders.https://doi.org/10.1186/s13578-024-01341-2PATL2 mutationTUT7CDC23mRNA storagemRNA decay |
| spellingShingle | Yin-Li Zhang Zhanhong Hu Huifang Jiang Jiamin Jin Yan Zhou Mengru Lai Peipei Ren Siya Liu Ying-Yi Zhang Yan Rong Wei Zheng Shen Zhang Xiaomei Tong Songying Zhang PATL2 mutations affect human oocyte maternal mRNA homeostasis and protein interactions in cell cycle regulation Cell & Bioscience PATL2 mutation TUT7 CDC23 mRNA storage mRNA decay |
| title | PATL2 mutations affect human oocyte maternal mRNA homeostasis and protein interactions in cell cycle regulation |
| title_full | PATL2 mutations affect human oocyte maternal mRNA homeostasis and protein interactions in cell cycle regulation |
| title_fullStr | PATL2 mutations affect human oocyte maternal mRNA homeostasis and protein interactions in cell cycle regulation |
| title_full_unstemmed | PATL2 mutations affect human oocyte maternal mRNA homeostasis and protein interactions in cell cycle regulation |
| title_short | PATL2 mutations affect human oocyte maternal mRNA homeostasis and protein interactions in cell cycle regulation |
| title_sort | patl2 mutations affect human oocyte maternal mrna homeostasis and protein interactions in cell cycle regulation |
| topic | PATL2 mutation TUT7 CDC23 mRNA storage mRNA decay |
| url | https://doi.org/10.1186/s13578-024-01341-2 |
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