The Role of RNA-specific Adenosine Deaminase 1 in Innate Immunity and Inflammation

doi:10.13560/j.cnki.biotech.bull.1985.2025-0608

Abstract

Abstract:

RNA-specific adenosine deaminase 1 (ADAR1) is one of the key enzymes in RNA editing, capable of catalyzing the conversion of adenosine (A) in double-stranded RNA (dsRNA) molecules to inosine (I), and plays a significant role in physiological processes such as immune regulation and inflammatory responses. The immune regulatory effect of ADAR1 is reflected in a dual mechanism. Firstly, it modifies the structure of dsRNA through RNA editing to prevent it from activating pattern recognition receptors and downstream effector proteins, thereby maintaining autoimmune tolerance. Secondly, by interacting with pattern recognition receptors such as RIG-I and MDA5 in a non-editing-dependent manner, it indirectly regulates the activation of signaling molecules such as NF-κB and IRF, thereby affecting the release of pro-inflammatory cytokines. In the inflammatory response, ADAR1 exerts anti-inflammatory effects through multiple pathways. On the one hand, it can edit viral or endogenous dsRNA, reducing the activation ability of dsRNA for RIG-I and MDA5, thereby inhibiting the excessive activation of antiviral inflammation. On the other hand, ADAR1 interacts directly with PKR to inhibit the phosphorylation of eIF2α, thereby balancing cell survival and inflammatory death. Meanwhile, ADAR1 can also edit endogenous dsRNA to block abnormal RNA degradation in the OAS-RNase L pathway and avoid autoinflammation triggered thereby. Furthermore, ADAR1 competes with ZBP1 for binding to Z-RNA, inhibiting RIPK3-MLKL-mediated programmed necrosis, thereby alleviating the inflammatory response caused by necrosis. These mechanisms provide a theoretical basis for the development of therapeutic strategies for inflammatory diseases. However, most of the above-mentioned studies have focused on human and mouse models, and their regulatory roles in inflammatory diseases in domestic animals remain unclear. Given the significant impact of inflammatory diseases on the livestock economy, this paper reviews the research on ADAR1 in terms of inflammation and immunity, and summarizes its important regulatory mechanisms, with the aim of laying the foundation for revealing the pathogenesis of inflammatory diseases in domestic animals such as mastitis in dairy cows and developing effective prevention and treatment strategies.

Key words: ADAR1, innate immunity, inflammation, RNA editing

LI Hui-hui, WANG Shu-jie, KANG Xiao-long. The Role of RNA-specific Adenosine Deaminase 1 in Innate Immunity and Inflammation[J]. Biotechnology Bulletin, 2026, 42(1): 42-50.

Figures/Tables 2

References 59

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