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Review
. 2023 Aug 17:14:1194884.
doi: 10.3389/fphar.2023.1194884. eCollection 2023.

Adenosine deaminase acting on RNA 1 (ADAR1) as crucial regulators in cardiovascular diseases: structures, pathogenesis, and potential therapeutic approach

Jieying Chen  1 , Junyan Jin  1   2 , Jun Jiang  1   2 , Yaping Wang  1   2
Affiliations
Review

Adenosine deaminase acting on RNA 1 (ADAR1) as crucial regulators in cardiovascular diseases: structures, pathogenesis, and potential therapeutic approach

Jieying Chen et al. Front Pharmacol. .

Abstract

Cardiovascular diseases (CVDs) are a group of diseases that have a major impact on global health and are the leading cause of death. A large number of chemical base modifications in ribonucleic acid (RNA) are associated with cardiovascular diseases. A variety of ribonucleic acid modifications exist in cells, among which adenosine deaminase-dependent modification is one of the most common ribonucleic acid modifications. Adenosine deaminase acting on ribonucleic acid 1 (Adenosine deaminase acting on RNA 1) is a widely expressed double-stranded ribonucleic acid adenosine deaminase that forms inosine (A-to-I) by catalyzing the deamination of adenosine at specific sites of the target ribonucleic acid. In this review, we provide a comprehensive overview of the structure of Adenosine deaminase acting on RNA 1 and summarize the regulatory mechanisms of ADAR1-mediated ribonucleic acid editing in cardiovascular diseases, indicating Adenosine deaminase acting on RNA 1 as a promising therapeutic target in cardiovascular diseases.

Keywords: ADAR1; RNA editing; cardiovascular diseases; potential therapeutic approach; target gene regulation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
ADAR1 protein has three domains (light green) that bind to dsRNA and a conserved catalytic deamination domain (purple) at the C-terminal. The difference is that ADAR1 p150 contains a Z-α domain (red), called Z-RNA, that binds to left-handed dsRNAs. The Zβ domain (yellow), which is homologous to the Zα structure, is separated from the Zα by a long linker at the N terminal of ADAR1, but its function remains unknown. ADAR1 p110 lacks the Z-α domain. In addition, most of the Adarl p150 was localized in the cytoplasm due to a nuclear export signal (NES; shown in green) segment in the Z-DNA binding domain near the N terminal. The nuclear localization signal (NLS; shown in blue) is present in both p150 and p110 isomers.
FIGURE 2
FIGURE 2
A figure about the roles of ADAR1 in cardiovascular diseases.
See this image and copyright information in PMC

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Grants and funding

This study was supported by the Medicine and Health Science and Technology Project of Zhejiang Province (No. 2022494325 to YW).