UFMylation safeguards human hepatocyte differentiation and liver homeostasis by regulating ribosome dissociation
Summary: Ribosomal UFMylation contributes to ribosome heterogeneity and is associated with ribosome-associated quality control at the endoplasmic reticulum. However, the specific pathophysiological functions of ribosomal UFMylation remain unknown. In this study, we systematically demonstrate the sig...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-05-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725004577 |
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| author | Shuchun Yang Li Wang Ran Gao Yanchang Li Duo Zhang Chenxi Wang Guang Liu Jie Na Ping Xu Xiaoyue Wang Yuyan Jia Yue Huang |
| author_facet | Shuchun Yang Li Wang Ran Gao Yanchang Li Duo Zhang Chenxi Wang Guang Liu Jie Na Ping Xu Xiaoyue Wang Yuyan Jia Yue Huang |
| author_sort | Shuchun Yang |
| collection | DOAJ |
| description | Summary: Ribosomal UFMylation contributes to ribosome heterogeneity and is associated with ribosome-associated quality control at the endoplasmic reticulum. However, the specific pathophysiological functions of ribosomal UFMylation remain unknown. In this study, we systematically demonstrate the significance of UFMylation in the differentiation and maturation of hepatocytes using human embryonic stem cell-derived hepatocyte-like cells and liver bud organoids as experimental platforms. We also develop a strategy to identify UFMylated substrates and confirm that RPL26 is a substrate in the liver. Additionally, we discover that mice with the Rpl26 c.395A>G (p.K132R) mutation are more susceptible to steatosis induced by a high-fat diet. Further investigations reveal a key role of CDK5RAP3 and RPL26 UFMylation in regulating ribosome dissociation. Our findings suggest that ribosome UFMylation serves as an important safeguard for liver development and homeostasis and may represent a potential therapeutic target for nonalcoholic fatty liver disease. |
| format | Article |
| id | doaj-art-9f31ccb04f6e4fa288cb14023dc0c8e9 |
| institution | OA Journals |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-9f31ccb04f6e4fa288cb14023dc0c8e92025-08-20T02:15:06ZengElsevierCell Reports2211-12472025-05-0144511568610.1016/j.celrep.2025.115686UFMylation safeguards human hepatocyte differentiation and liver homeostasis by regulating ribosome dissociationShuchun Yang0Li Wang1Ran Gao2Yanchang Li3Duo Zhang4Chenxi Wang5Guang Liu6Jie Na7Ping Xu8Xiaoyue Wang9Yuyan Jia10Yue Huang11State Key Laboratory of Common Mechanism Research for Major Disease, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China; Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, ChinaState Key Laboratory of Common Mechanism Research for Major Disease, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China; Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, ChinaState Key Laboratory of Common Mechanism Research for Major Disease, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, ChinaState Key Laboratory of Medical Proteomics, Beijng Proteome Research Center, National Center for Protein Sciences (Beijing), Research Unit of Proteomics & Research and Development of New Drugs of Chinese Academy of Medical Sciences, Institute of Lifeomics, Beijing 102206, ChinaState Key Laboratory of Common Mechanism Research for Major Disease, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China; Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, ChinaState Key Laboratory of Common Mechanism Research for Major Disease, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China; Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, ChinaState Key Laboratory of Common Mechanism Research for Major Disease, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China; Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, ChinaCenter for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua University, Beijing, ChinaState Key Laboratory of Medical Proteomics, Beijng Proteome Research Center, National Center for Protein Sciences (Beijing), Research Unit of Proteomics & Research and Development of New Drugs of Chinese Academy of Medical Sciences, Institute of Lifeomics, Beijing 102206, ChinaState Key Laboratory of Common Mechanism Research for Major Disease, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, ChinaState Key Laboratory of Common Mechanism Research for Major Disease, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China; Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China; Corresponding authorState Key Laboratory of Common Mechanism Research for Major Disease, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China; Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China; Corresponding authorSummary: Ribosomal UFMylation contributes to ribosome heterogeneity and is associated with ribosome-associated quality control at the endoplasmic reticulum. However, the specific pathophysiological functions of ribosomal UFMylation remain unknown. In this study, we systematically demonstrate the significance of UFMylation in the differentiation and maturation of hepatocytes using human embryonic stem cell-derived hepatocyte-like cells and liver bud organoids as experimental platforms. We also develop a strategy to identify UFMylated substrates and confirm that RPL26 is a substrate in the liver. Additionally, we discover that mice with the Rpl26 c.395A>G (p.K132R) mutation are more susceptible to steatosis induced by a high-fat diet. Further investigations reveal a key role of CDK5RAP3 and RPL26 UFMylation in regulating ribosome dissociation. Our findings suggest that ribosome UFMylation serves as an important safeguard for liver development and homeostasis and may represent a potential therapeutic target for nonalcoholic fatty liver disease.http://www.sciencedirect.com/science/article/pii/S2211124725004577CP: MetabolismCP: Molecular biology |
| spellingShingle | Shuchun Yang Li Wang Ran Gao Yanchang Li Duo Zhang Chenxi Wang Guang Liu Jie Na Ping Xu Xiaoyue Wang Yuyan Jia Yue Huang UFMylation safeguards human hepatocyte differentiation and liver homeostasis by regulating ribosome dissociation Cell Reports CP: Metabolism CP: Molecular biology |
| title | UFMylation safeguards human hepatocyte differentiation and liver homeostasis by regulating ribosome dissociation |
| title_full | UFMylation safeguards human hepatocyte differentiation and liver homeostasis by regulating ribosome dissociation |
| title_fullStr | UFMylation safeguards human hepatocyte differentiation and liver homeostasis by regulating ribosome dissociation |
| title_full_unstemmed | UFMylation safeguards human hepatocyte differentiation and liver homeostasis by regulating ribosome dissociation |
| title_short | UFMylation safeguards human hepatocyte differentiation and liver homeostasis by regulating ribosome dissociation |
| title_sort | ufmylation safeguards human hepatocyte differentiation and liver homeostasis by regulating ribosome dissociation |
| topic | CP: Metabolism CP: Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725004577 |
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