Dysregulated RBM24 phosphorylation impairs APOE translation underlying psychological stress-induced cardiovascular disease
Abstract Psychological stress contributes to cardiovascular disease (CVD) and sudden cardiac death, yet its molecular basis remains obscure. RNA binding protein RBM24 plays a critical role in cardiac development, rhythm regulation, and cellular stress. Here, we show that psychological stress activat...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54519-0 |
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| author | He Yang Lei Sun Xuemei Bai Bingcheng Cai Zepeng Tu Chen Fang Yusheng Bian Xiaoyu Zhang Xudong Han Dayin Lv Chi Zhang Bo Li Shaoxiang Luo Bingbing Du Lan Li Yufeng Yao Zhiqiang Dong Zhuowei Huang Guanhua Su Hui Li Qing K. Wang Min Zhang |
| author_facet | He Yang Lei Sun Xuemei Bai Bingcheng Cai Zepeng Tu Chen Fang Yusheng Bian Xiaoyu Zhang Xudong Han Dayin Lv Chi Zhang Bo Li Shaoxiang Luo Bingbing Du Lan Li Yufeng Yao Zhiqiang Dong Zhuowei Huang Guanhua Su Hui Li Qing K. Wang Min Zhang |
| author_sort | He Yang |
| collection | DOAJ |
| description | Abstract Psychological stress contributes to cardiovascular disease (CVD) and sudden cardiac death, yet its molecular basis remains obscure. RNA binding protein RBM24 plays a critical role in cardiac development, rhythm regulation, and cellular stress. Here, we show that psychological stress activates RBM24 S181 phosphorylation through eIF4E2-GSK3β signaling, which causally links psychological stress to CVD by promoting APOE translation (apolipoprotein E). Using an Rbm24 S181A KI mouse model, we show that impaired S181 phosphorylation leads to cardiac contractile dysfunction, atrial fibrillation, dyslipidemia, reduced muscle strength, behavioral abnormalities, and sudden death under acute and chronic psychological stressors. The impaired S181 phosphorylation of RBM24 inhibits cardiac translation, including APOE translation. Notably, cardiomyocyte-specific expression of APOE rescues cardiac electrophysiological abnormalities and contractile dysfunction, through preventing ROS stress and mitochondrial dysfunction. Moreover, RBM24-S181 phosphorylation acts as a serum marker for chronic stress in human. These results provide a functional link between RBM24 phosphorylation, eIF4E-regulated APOE translation, and psychological-stress-induced CVD. |
| format | Article |
| id | doaj-art-a1c41a7c1b344ffda816def7275b5e2b |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-a1c41a7c1b344ffda816def7275b5e2b2024-11-24T12:32:51ZengNature PortfolioNature Communications2041-17232024-11-0115112110.1038/s41467-024-54519-0Dysregulated RBM24 phosphorylation impairs APOE translation underlying psychological stress-induced cardiovascular diseaseHe Yang0Lei Sun1Xuemei Bai2Bingcheng Cai3Zepeng Tu4Chen Fang5Yusheng Bian6Xiaoyu Zhang7Xudong Han8Dayin Lv9Chi Zhang10Bo Li11Shaoxiang Luo12Bingbing Du13Lan Li14Yufeng Yao15Zhiqiang Dong16Zhuowei Huang17Guanhua Su18Hui Li19Qing K. Wang20Min Zhang21College of Biomedicine and Health, College of Life science and Technology, Huazhong Agricultural UniversityCollege of Biomedicine and Health, College of Life science and Technology, Huazhong Agricultural UniversityCenter for Human Genome Research, College of Life Science and Technology, Key Laboratory of Molecular Biophysics of the Ministry of Education, Huazhong University of Science and TechnologyCollege of Biomedicine and Health, College of Life science and Technology, Huazhong Agricultural UniversityCollege of Biomedicine and Health, College of Life science and Technology, Huazhong Agricultural UniversityCenter for Human Genome Research, College of Life Science and Technology, Key Laboratory of Molecular Biophysics of the Ministry of Education, Huazhong University of Science and TechnologyCollege of Biomedicine and Health, College of Life science and Technology, Huazhong Agricultural UniversityCenter for Human Genome Research, College of Life Science and Technology, Key Laboratory of Molecular Biophysics of the Ministry of Education, Huazhong University of Science and TechnologyCollege of Biomedicine and Health, College of Life science and Technology, Huazhong Agricultural UniversityCenter for Human Genome Research, College of Life Science and Technology, Key Laboratory of Molecular Biophysics of the Ministry of Education, Huazhong University of Science and TechnologyCenter for Human Genome Research, College of Life Science and Technology, Key Laboratory of Molecular Biophysics of the Ministry of Education, Huazhong University of Science and TechnologyCollege of Biomedicine and Health, College of Life science and Technology, Huazhong Agricultural UniversityWuhan Huamei Biotech Co., LtdCollege of Biomedicine and Health, College of Life science and Technology, Huazhong Agricultural UniversityCollege of Biomedicine and Health, College of Life science and Technology, Huazhong Agricultural UniversityCenter for Human Genome Research, College of Life Science and Technology, Key Laboratory of Molecular Biophysics of the Ministry of Education, Huazhong University of Science and TechnologyCollege of Biomedicine and Health, College of Life science and Technology, Huazhong Agricultural UniversityAffiliated Wuhan Mental Health Center, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCenter for Human Genome Research, College of Life Science and Technology, Key Laboratory of Molecular Biophysics of the Ministry of Education, Huazhong University of Science and TechnologyCenter for Human Genome Research, College of Life Science and Technology, Key Laboratory of Molecular Biophysics of the Ministry of Education, Huazhong University of Science and TechnologyCollege of Biomedicine and Health, College of Life science and Technology, Huazhong Agricultural UniversityAbstract Psychological stress contributes to cardiovascular disease (CVD) and sudden cardiac death, yet its molecular basis remains obscure. RNA binding protein RBM24 plays a critical role in cardiac development, rhythm regulation, and cellular stress. Here, we show that psychological stress activates RBM24 S181 phosphorylation through eIF4E2-GSK3β signaling, which causally links psychological stress to CVD by promoting APOE translation (apolipoprotein E). Using an Rbm24 S181A KI mouse model, we show that impaired S181 phosphorylation leads to cardiac contractile dysfunction, atrial fibrillation, dyslipidemia, reduced muscle strength, behavioral abnormalities, and sudden death under acute and chronic psychological stressors. The impaired S181 phosphorylation of RBM24 inhibits cardiac translation, including APOE translation. Notably, cardiomyocyte-specific expression of APOE rescues cardiac electrophysiological abnormalities and contractile dysfunction, through preventing ROS stress and mitochondrial dysfunction. Moreover, RBM24-S181 phosphorylation acts as a serum marker for chronic stress in human. These results provide a functional link between RBM24 phosphorylation, eIF4E-regulated APOE translation, and psychological-stress-induced CVD.https://doi.org/10.1038/s41467-024-54519-0 |
| spellingShingle | He Yang Lei Sun Xuemei Bai Bingcheng Cai Zepeng Tu Chen Fang Yusheng Bian Xiaoyu Zhang Xudong Han Dayin Lv Chi Zhang Bo Li Shaoxiang Luo Bingbing Du Lan Li Yufeng Yao Zhiqiang Dong Zhuowei Huang Guanhua Su Hui Li Qing K. Wang Min Zhang Dysregulated RBM24 phosphorylation impairs APOE translation underlying psychological stress-induced cardiovascular disease Nature Communications |
| title | Dysregulated RBM24 phosphorylation impairs APOE translation underlying psychological stress-induced cardiovascular disease |
| title_full | Dysregulated RBM24 phosphorylation impairs APOE translation underlying psychological stress-induced cardiovascular disease |
| title_fullStr | Dysregulated RBM24 phosphorylation impairs APOE translation underlying psychological stress-induced cardiovascular disease |
| title_full_unstemmed | Dysregulated RBM24 phosphorylation impairs APOE translation underlying psychological stress-induced cardiovascular disease |
| title_short | Dysregulated RBM24 phosphorylation impairs APOE translation underlying psychological stress-induced cardiovascular disease |
| title_sort | dysregulated rbm24 phosphorylation impairs apoe translation underlying psychological stress induced cardiovascular disease |
| url | https://doi.org/10.1038/s41467-024-54519-0 |
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