YTHDC1-mediated microRNA maturation is essential for hematopoietic stem cells maintenance
Abstract YTHDC1, a reader of N6-methyladenosine (m6A) modifications on RNA, is posited to exert significant influence over RNA metabolism. Despite its recognized importance, the precise function and underlying mechanisms of YTHDC1 in the preservation of normal hematopoietic stem cell (HSCs) homeosta...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2024-10-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-024-02203-z |
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| author | Hongna Zuo Jin Liu Bin Shen Yue Sheng Zhenyu Ju Hu Wang |
| author_facet | Hongna Zuo Jin Liu Bin Shen Yue Sheng Zhenyu Ju Hu Wang |
| author_sort | Hongna Zuo |
| collection | DOAJ |
| description | Abstract YTHDC1, a reader of N6-methyladenosine (m6A) modifications on RNA, is posited to exert significant influence over RNA metabolism. Despite its recognized importance, the precise function and underlying mechanisms of YTHDC1 in the preservation of normal hematopoietic stem cell (HSCs) homeostasis remain elusive. Here, we investigated the role of YTHDC1 in normal hematopoiesis and HSCs maintenance in vivo. Utilizing conditional Ythdc1 knockout mice and Ythdc1/Mettl3 double knockout mice, we demonstrated that YTHDC1 is required for HSCs maintenance and self-renewal by regulating microRNA maturation. YTHDC1 deficiency resulted in HSCs apoptosis. Furthermore, we uncovered that YTHDC1 interacts with HP1BP3, a nuclear RNA binding protein involved in microRNA maturation. Deletion of YTHDC1 brought about significant alterations in microRNA levels. However, over-expression of mir-125b, mir-99b, and let-7e partially rescued the functional defect of YTHDC1-null HSCs. Taken together, these findings indicated that the nuclear protein YTHDC1-HP1BP3-microRNA maturation axis is essential for the long-term maintenance of HSCs. |
| format | Article |
| id | doaj-art-6d8fe684599542cb9b2bccf5dd3f329d |
| institution | OA Journals |
| issn | 2058-7716 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj-art-6d8fe684599542cb9b2bccf5dd3f329d2025-08-20T02:17:45ZengNature Publishing GroupCell Death Discovery2058-77162024-10-0110111310.1038/s41420-024-02203-zYTHDC1-mediated microRNA maturation is essential for hematopoietic stem cells maintenanceHongna Zuo0Jin Liu1Bin Shen2Yue Sheng3Zhenyu Ju4Hu Wang5Department of Hematology, the Second Xiangya Hospital, Central South UniversityDepartment of Hematology, the Second Xiangya Hospital, Central South UniversityDepartment of Histology and Embryology, State Key Laboratory of Reproductive Medicine, Nanjing Medical UniversityDepartment of Hematology, the Second Xiangya Hospital, Central South UniversityMOE Key Laboratory of Regenerative Medicine, Institute of Aging and Regenerative Medicine, Jinan UniversityZhejiang Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, The Third People’s Hospital of Deqing, Department of Cardiology, Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal UniversityAbstract YTHDC1, a reader of N6-methyladenosine (m6A) modifications on RNA, is posited to exert significant influence over RNA metabolism. Despite its recognized importance, the precise function and underlying mechanisms of YTHDC1 in the preservation of normal hematopoietic stem cell (HSCs) homeostasis remain elusive. Here, we investigated the role of YTHDC1 in normal hematopoiesis and HSCs maintenance in vivo. Utilizing conditional Ythdc1 knockout mice and Ythdc1/Mettl3 double knockout mice, we demonstrated that YTHDC1 is required for HSCs maintenance and self-renewal by regulating microRNA maturation. YTHDC1 deficiency resulted in HSCs apoptosis. Furthermore, we uncovered that YTHDC1 interacts with HP1BP3, a nuclear RNA binding protein involved in microRNA maturation. Deletion of YTHDC1 brought about significant alterations in microRNA levels. However, over-expression of mir-125b, mir-99b, and let-7e partially rescued the functional defect of YTHDC1-null HSCs. Taken together, these findings indicated that the nuclear protein YTHDC1-HP1BP3-microRNA maturation axis is essential for the long-term maintenance of HSCs.https://doi.org/10.1038/s41420-024-02203-z |
| spellingShingle | Hongna Zuo Jin Liu Bin Shen Yue Sheng Zhenyu Ju Hu Wang YTHDC1-mediated microRNA maturation is essential for hematopoietic stem cells maintenance Cell Death Discovery |
| title | YTHDC1-mediated microRNA maturation is essential for hematopoietic stem cells maintenance |
| title_full | YTHDC1-mediated microRNA maturation is essential for hematopoietic stem cells maintenance |
| title_fullStr | YTHDC1-mediated microRNA maturation is essential for hematopoietic stem cells maintenance |
| title_full_unstemmed | YTHDC1-mediated microRNA maturation is essential for hematopoietic stem cells maintenance |
| title_short | YTHDC1-mediated microRNA maturation is essential for hematopoietic stem cells maintenance |
| title_sort | ythdc1 mediated microrna maturation is essential for hematopoietic stem cells maintenance |
| url | https://doi.org/10.1038/s41420-024-02203-z |
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