ADAR1: from Basic Mechanisms to Inhibitors

Overview

Journal Trends Cell Biol

Specialty Cell Biology

Date 2024 Jul 19

PMID 39030076

Authors

Jan Rehwinkel

Parinaz Mehdipour

Affiliations

Soon will be listed here.

Abstract

Adenosine deaminase acting on RNA 1 (ADAR1) converts adenosine to inosine in double-stranded RNA (dsRNA) molecules, a process known as A-to-I editing. ADAR1 deficiency in humans and mice results in profound inflammatory diseases characterised by the spontaneous induction of innate immunity. In cells lacking ADAR1, unedited RNAs activate RNA sensors. These include melanoma differentiation-associated gene 5 (MDA5) that induces the expression of cytokines, particularly type I interferons (IFNs), protein kinase R (PKR), oligoadenylate synthase (OAS), and Z-DNA/RNA binding protein 1 (ZBP1). Immunogenic RNAs 'defused' by ADAR1 may include transcripts from repetitive elements and other long duplex RNAs. Here, we review these recent fundamental discoveries and discuss implications for human diseases. Some tumours depend on ADAR1 to escape immune surveillance, opening the possibility of unleashing anticancer therapies with ADAR1 inhibitors.

Citing Articles

A Wonderful Journey: The Diverse Roles of Adenosine Deaminase Action on RNA 1 (ADAR1) in Central Nervous System Diseases.

Cheng L, Liu Z, Shen C, Xiong Y, Shin S, Hwang Y CNS Neurosci Ther. 2025; 31(1):e70208.

PMID: 39753993 PMC: 11702419. DOI: 10.1111/cns.70208.

ADAR1 could be a potential diagnostic target for intrauterine infection patients.

Nakamura K, Shigeyasu K, Vu T, Maki J, Okamoto K, Masuyama H Sci Rep. 2024; 14(1):29419.

PMID: 39592688 PMC: 11599928. DOI: 10.1038/s41598-024-81097-4.

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