Alternative cleavage and polyadenylation: key regulatory mechanisms in health and disease
Alternative polyadenylation (APA) is a critical post-transcriptional regulatory mechanism that generates diverse mRNA isoforms by selecting different polyadenylation sites within pre-mRNAs, thereby modulating the length of the 3’ untranslated region (3’ UTR), thereby fine-tuning gene expression and...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | RNA Biology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/15476286.2025.2529033 |
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| author | Ying Zhang Zikun Huang Weiqing Lu Zhaoyong Liu |
| author_facet | Ying Zhang Zikun Huang Weiqing Lu Zhaoyong Liu |
| author_sort | Ying Zhang |
| collection | DOAJ |
| description | Alternative polyadenylation (APA) is a critical post-transcriptional regulatory mechanism that generates diverse mRNA isoforms by selecting different polyadenylation sites within pre-mRNAs, thereby modulating the length of the 3’ untranslated region (3’ UTR), thereby fine-tuning gene expression and protein synthesis. APA regulation involves conserved cis-acting elements, trans-acting factors, and key protein complexes such as CPSF and CSTF, influenced by the cellular context and various RNA-binding proteins. To address the complexity of APA, comprehensive methodologies and computational tools have been developed, leading to extensive APA databases with detailed biological annotations. Recent advancements in high-throughput sequencing and single-cell technologies have enhanced our understanding of APA’s dynamic regulation across tissues and developmental stages, revealing its significant impact on cellular heterogeneity and disease progression. APA plays essential roles in numerous physiological processes, including neuronal homoeostasis, immune regulation, cardiovascular and vascular development, myogenesis, and metabolism. Dysregulation of APA is associated with a wide range of diseases, including neurodegenerative disorders, autoimmune conditions, cardiovascular diseases, metabolic syndromes, and genetic disorders. Clinically, targeting APA regulatory mechanisms offers promising opportunities for therapeutic interventions and the development of personalized medical strategies. This review highlights the pivotal role of APA in gene regulation and disease, emphasizing the need for continued research to unravel its complex mechanisms and leverage its potential in advancing precision medicine. |
| format | Article |
| id | doaj-art-c8dfa3ceaaf94ebc8a81f90a1bb20ddc |
| institution | Matheson Library |
| issn | 1547-6286 1555-8584 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | RNA Biology |
| spelling | doaj-art-c8dfa3ceaaf94ebc8a81f90a1bb20ddc2025-07-09T10:23:26ZengTaylor & Francis GroupRNA Biology1547-62861555-85842025-12-0122113310.1080/15476286.2025.2529033Alternative cleavage and polyadenylation: key regulatory mechanisms in health and diseaseYing Zhang0Zikun Huang1Weiqing Lu2Zhaoyong Liu3Department of Radiotherapy, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, ChinaDepartment of Orthopaedics, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, ChinaDepartment of Radiotherapy, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, ChinaDepartment of Orthopaedics, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, ChinaAlternative polyadenylation (APA) is a critical post-transcriptional regulatory mechanism that generates diverse mRNA isoforms by selecting different polyadenylation sites within pre-mRNAs, thereby modulating the length of the 3’ untranslated region (3’ UTR), thereby fine-tuning gene expression and protein synthesis. APA regulation involves conserved cis-acting elements, trans-acting factors, and key protein complexes such as CPSF and CSTF, influenced by the cellular context and various RNA-binding proteins. To address the complexity of APA, comprehensive methodologies and computational tools have been developed, leading to extensive APA databases with detailed biological annotations. Recent advancements in high-throughput sequencing and single-cell technologies have enhanced our understanding of APA’s dynamic regulation across tissues and developmental stages, revealing its significant impact on cellular heterogeneity and disease progression. APA plays essential roles in numerous physiological processes, including neuronal homoeostasis, immune regulation, cardiovascular and vascular development, myogenesis, and metabolism. Dysregulation of APA is associated with a wide range of diseases, including neurodegenerative disorders, autoimmune conditions, cardiovascular diseases, metabolic syndromes, and genetic disorders. Clinically, targeting APA regulatory mechanisms offers promising opportunities for therapeutic interventions and the development of personalized medical strategies. This review highlights the pivotal role of APA in gene regulation and disease, emphasizing the need for continued research to unravel its complex mechanisms and leverage its potential in advancing precision medicine.https://www.tandfonline.com/doi/10.1080/15476286.2025.2529033APAdisease3’ UTRdevelopmentRNA-binding protein |
| spellingShingle | Ying Zhang Zikun Huang Weiqing Lu Zhaoyong Liu Alternative cleavage and polyadenylation: key regulatory mechanisms in health and disease RNA Biology APA disease 3’ UTR development RNA-binding protein |
| title | Alternative cleavage and polyadenylation: key regulatory mechanisms in health and disease |
| title_full | Alternative cleavage and polyadenylation: key regulatory mechanisms in health and disease |
| title_fullStr | Alternative cleavage and polyadenylation: key regulatory mechanisms in health and disease |
| title_full_unstemmed | Alternative cleavage and polyadenylation: key regulatory mechanisms in health and disease |
| title_short | Alternative cleavage and polyadenylation: key regulatory mechanisms in health and disease |
| title_sort | alternative cleavage and polyadenylation key regulatory mechanisms in health and disease |
| topic | APA disease 3’ UTR development RNA-binding protein |
| url | https://www.tandfonline.com/doi/10.1080/15476286.2025.2529033 |
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