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ADAR1p150 Forms a Complex with Dicer to Promote miRNA-222 Activity and Regulate PTEN Expression in CVB3-Induced Viral
Xincai Zhang1, Xiangting Gao2, Jun Hu3
1Institute of Forensic Medicine, Soochow University, Suzhou 215021, China. xczhang1@stu.suda.edu.cn.
Abstract:
Adenosine deaminases acting on RNA (ADAR) are enzymes that regulate RNA metabolism through post-transcriptional mechanisms. ADAR1 is involved in a variety of pathological conditions including inflammation, cancer, and the host defense against viral infections. However, the role of ADAR1p150 in vascular disease remains unclear. In this study, we examined the expression of ADAR1p150 and its role in viral myocarditis (VMC) in a mouse model. VMC mouse cardiomyocytes showed significantly higher expression of ADAR1p150 compared to the control samples. Coimmunoprecipitation verified that ADAR1p150 forms a complex with Dicer in VMC. miRNA-222, which is involved in many cardiac diseases, is highly expressed in cardiomyocytes in VMC. In addition, the expression of miRNA-222 was promoted by ADAR1p150/Dicer. Among the target genes of miRNA-222, the expression of phosphatase-and-tensin (PTEN) protein was significantly reduced in VMC. By using a bioinformatics tool, we found a potential binding site of miRNA-222 on the PTEN gene's 3'-UTR, suggesting that miRNA-222 might play a regulatory role. In cultured cells, miR-222 suppressed PTEN expression. Our findings suggest that ADAR1p150 plays a key role in complexing with Dicer and promoting the expression of miRNA-222, the latter of which suppresses the expression of the target gene PTEN during VMC. Our work reveals a previously unknown role of ADAR1p150 in gene expression in VMC.
Insights
Adenosine deaminases acting on RNA 1 p150 (ADAR1p150) promotes microRNA-222 expression in viral myocarditis. This leads to reduced PTEN protein, revealing ADAR1p150
Area of Science:
- Molecular Biology
- RNA Metabolism
- Cardiovascular Research
Background:
- Adenosine deaminases acting on RNA (ADAR) enzymes regulate RNA metabolism.
- ADAR1 is implicated in inflammation, cancer, and antiviral defense.
- The specific role of ADAR1p150 in vascular disease, particularly viral myocarditis (VMC), is not well understood.
Purpose of the Study:
- To investigate the expression and function of ADAR1p150 in viral myocarditis (VMC).
- To elucidate the molecular mechanisms involving ADAR1p150 in the pathogenesis of VMC.
Main Methods:
- Utilized a mouse model of viral myocarditis (VMC).
- Examined ADAR1p150 expression in cardiomyocytes using techniques like coimmunoprecipitation.
- Analyzed miRNA-222 and PTEN expression and their interactions using bioinformatics and cell culture experiments.
Main Results:
- ADAR1p150 expression was significantly elevated in VMC cardiomyocytes.
- ADAR1p150 was found to complex with Dicer and promote miRNA-222 expression in VMC.
- miRNA-222 expression was increased in VMC, leading to decreased PTEN protein levels.
- Bioinformatics and cell culture confirmed miRNA-222 targets PTEN, suppressing its expression.
Conclusions:
- ADAR1p150 plays a critical role in VMC by complexing with Dicer and upregulating miRNA-222.
- The ADAR1p150/miRNA-222 axis suppresses PTEN expression in VMC.
- This study uncovers a novel function of ADAR1p150 in regulating gene expression during viral myocarditis.
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