Zinc Finger Protein Znf296 Is a Cardiac-Specific Splicing Regulator Required for Cardiomyocyte Formation.
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| Main Authors: | , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
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The American journal of pathology
2025
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| _version_ | 1868266228819165186 |
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| author | Li, Xianpeng Yang, Shuaiqi Wang, Lu Zhang, Xiangmin Zhang, Ailong Wang, Yunchao Shi, De-Li Li, Hongyan |
| author_facet | Li, Xianpeng Yang, Shuaiqi Wang, Lu Zhang, Xiangmin Zhang, Ailong Wang, Yunchao Shi, De-Li Li, Hongyan Li, Xianpeng Yang, Shuaiqi Wang, Lu Zhang, Xiangmin Zhang, Ailong Wang, Yunchao Shi, De-Li Li, Hongyan |
| collection | PubMed - marine biology |
| contents | Zinc Finger Protein Znf296 Is a Cardiac-Specific Splicing Regulator Required for Cardiomyocyte Formation. Li, Xianpeng Yang, Shuaiqi Wang, Lu Zhang, Xiangmin Zhang, Ailong Wang, Yunchao Shi, De-Li Li, Hongyan Animals Zebrafish Myocytes, Cardiac Humans Zebrafish Proteins Alternative Splicing Heart Zinc Fingers Gene Expression Regulation, Developmental Transcription Factors Heart formation and function are tightly regulated at transcriptional and post-transcriptional levels. The dysfunction of cardiac cell-specific regulatory genes leads to various heart diseases. Heart failure is one of the most severe and complex cardiovascular diseases, which could be fatal if not treated promptly. However, the exact causes of heart failure are still unclear, especially at the level of single-gene causation. Here, an essential role was uncovered for the zinc finger protein Znf296 in heart development and cardiac contractile function. Specifically, znf296-deficient zebrafish embryos displayed heart defects characterized by decreased systolic and diastolic capacities of the ventricle and atrium. This was associated with reduced numbers and disrupted structural integrity of cardiomyocytes, including disorganized cytoskeleton and absence of sarcomeres. Mechanistically, the loss of Znf296 altered the alternative splicing of a subset of genes important for heart development and disease, such as mef2ca, sparc, tpm2, camk2g1, tnnt3b, and pdlim5b. Furthermore, Znf296 biochemically and functionally interacted with myelin transcription factor 1-like, a (Myt1la) in regulating cardiac-specific splicing and heart development. Importantly, ZNF296 also regulated alternative splicing in human cardiomyocytes to maintain structural integrity. These results suggest that Znf296 plays a conserved role for the differentiation of cardiomyocytes and the proper function of the cardiovascular system. |
| format | Artículo científico |
| id | pubmed_40122456 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | The American journal of pathology |
| record_format | pubmed |
| spellingShingle | Zinc Finger Protein Znf296 Is a Cardiac-Specific Splicing Regulator Required for Cardiomyocyte Formation. Li, Xianpeng Yang, Shuaiqi Wang, Lu Zhang, Xiangmin Zhang, Ailong Wang, Yunchao Shi, De-Li Li, Hongyan Animals Zebrafish Myocytes, Cardiac Humans Zebrafish Proteins Alternative Splicing Heart Zinc Fingers Gene Expression Regulation, Developmental Transcription Factors Zinc Finger Protein Znf296 Is a Cardiac-Specific Splicing Regulator Required for Cardiomyocyte Formation. Li, Xianpeng Yang, Shuaiqi Wang, Lu Zhang, Xiangmin Zhang, Ailong Wang, Yunchao Shi, De-Li Li, Hongyan Animals Zebrafish Myocytes, Cardiac Humans Zebrafish Proteins Alternative Splicing Heart Zinc Fingers Gene Expression Regulation, Developmental Transcription Factors Heart formation and function are tightly regulated at transcriptional and post-transcriptional levels. The dysfunction of cardiac cell-specific regulatory genes leads to various heart diseases. Heart failure is one of the most severe and complex cardiovascular diseases, which could be fatal if not treated promptly. However, the exact causes of heart failure are still unclear, especially at the level of single-gene causation. Here, an essential role was uncovered for the zinc finger protein Znf296 in heart development and cardiac contractile function. Specifically, znf296-deficient zebrafish embryos displayed heart defects characterized by decreased systolic and diastolic capacities of the ventricle and atrium. This was associated with reduced numbers and disrupted structural integrity of cardiomyocytes, including disorganized cytoskeleton and absence of sarcomeres. Mechanistically, the loss of Znf296 altered the alternative splicing of a subset of genes important for heart development and disease, such as mef2ca, sparc, tpm2, camk2g1, tnnt3b, and pdlim5b. Furthermore, Znf296 biochemically and functionally interacted with myelin transcription factor 1-like, a (Myt1la) in regulating cardiac-specific splicing and heart development. Importantly, ZNF296 also regulated alternative splicing in human cardiomyocytes to maintain structural integrity. These results suggest that Znf296 plays a conserved role for the differentiation of cardiomyocytes and the proper function of the cardiovascular system. |
| title | Zinc Finger Protein Znf296 Is a Cardiac-Specific Splicing Regulator Required for Cardiomyocyte Formation. |
| topic | Animals Zebrafish Myocytes, Cardiac Humans Zebrafish Proteins Alternative Splicing Heart Zinc Fingers Gene Expression Regulation, Developmental Transcription Factors |
| url | https://pubmed.ncbi.nlm.nih.gov/40122456/ |