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Silencing mouse circular RNA circSlc8a1 by circular antisense cA-circSlc8a1 induces cardiac hepatopathy.
Wu, Nan; Li, Feiya; Yang, Weining; Du, William W; Awan, Faryal Mehwish; Zhang, Chao; Lyu, Juanjuan; Misir, Sema; Zeng, Kaixuan; Eshaghi, Esra; Yang, Burton B.
Afiliación
  • Wu N; Sunnybrook Research Institute, Toronto, ON M4N3M5, Canada.
  • Li F; Sunnybrook Research Institute, Toronto, ON M4N3M5, Canada.
  • Yang W; Sunnybrook Research Institute, Toronto, ON M4N3M5, Canada.
  • Du WW; Sunnybrook Research Institute, Toronto, ON M4N3M5, Canada.
  • Awan FM; Sunnybrook Research Institute, Toronto, ON M4N3M5, Canada; Department of Medical Lab Technology, the University of Haripur (UOH), Haripur, Pakistan.
  • Zhang C; Sunnybrook Research Institute, Toronto, ON M4N3M5, Canada.
  • Lyu J; Sunnybrook Research Institute, Toronto, ON M4N3M5, Canada.
  • Misir S; Sunnybrook Research Institute, Toronto, ON M4N3M5, Canada.
  • Zeng K; Sunnybrook Research Institute, Toronto, ON M4N3M5, Canada.
  • Eshaghi E; Sunnybrook Research Institute, Toronto, ON M4N3M5, Canada.
  • Yang BB; Sunnybrook Research Institute, Toronto, ON M4N3M5, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada. Electronic address: byang@sri.utoronto.ca.
Mol Ther ; 31(6): 1688-1704, 2023 Jun 07.
Article en En | MEDLINE | ID: mdl-36245125
Circular RNAs (circRNAs) are a group of non-coding RNAs with a unique circular structure generated by back-splicing. It is acknowledged that circRNAs play critical roles in cardiovascular diseases. However, functional studies of circRNAs were impeded due to lack of effective in vivo silencing approaches. Since most circRNAs are produced by protein-coding transcripts, gene editing typically affects the coding activity of the parental genes. In this study, we developed a circular antisense RNA (cA-circSlc8a1) that could silence the highly expressed circRNA circSlc8a1 in the mouse heart but not its parental Slc8a1 linear mRNA. Transgenic cA-circSlc8a1 mice developed congestive heart failure resulting in a significant increase in the body weight secondary to peripheral edema and congestive hepatopathy. To further test the role of circSlc8a1, we generated transgenic mice overexpressing circSlc8a1 and observed a protective effect of circSlc8a1 in a pressure overload model. Mechanistically, we found that circSlc8a1 translocated into mitochondria to drive ATP synthesis. While establishing a transgenic murine model for antisense-mediated circRNA silencing without interfering with the parental linear RNA, our finding revealed the essential role of circSlc8a1 in maintaining heart function and may lay the groundwork of using the circular antisense RNA as a potential gene therapy approach for cardiovascular diseases.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Cardiovasculares / ARN sin Sentido / Intercambiador de Sodio-Calcio / ARN Circular / Insuficiencia Cardíaca Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Mol Ther Asunto de la revista: BIOLOGIA MOLECULAR / TERAPEUTICA Año: 2023 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Cardiovasculares / ARN sin Sentido / Intercambiador de Sodio-Calcio / ARN Circular / Insuficiencia Cardíaca Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Mol Ther Asunto de la revista: BIOLOGIA MOLECULAR / TERAPEUTICA Año: 2023 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos