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The role of ADAR1 through and beyond its editing activity in cancer.

ABSTRACT: Adenosine-to-inosine (A-to-I) editing of RNA, catalyzed by adenosine deaminase acting on RNA (ADAR) enzymes, is a prevalent RNA modification in mammals. It has been shown that A-to-I editing plays a critical role in multiple diseases, such as cardiovascular disease, neurological disorder, and particularly cancer. ADARs are the family of enzymes, including ADAR1, ADAR2, and ADAR3, that catalyze the occurrence of A-to-I editing. Notably, A-to-I editing is mainly catalyzed by ADAR1. Given the significance of A-to-I editing in disease development, it is important to unravel the complex roles of ADAR1 in cancer for the development of novel therapeutic interventions.In this review, we briefly describe the progress of research on A-to-I editing and ADARs in cancer, mainly focusing on the role of ADAR1 in cancer from both editing-dependent and independent perspectives. In addition, we also summarized the factors affecting the expression and editing activity of ADAR1 in cancer.

SUBMITTER: Jiao Y

PROVIDER: S-EPMC10795376 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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The role of ADAR1 through and beyond its editing activity in cancer.

Jiao Yue Y Xu Yuqin Y Liu Chengbin C Miao Rui R Liu Chunyan C Wang Yilong Y Liu Jiao J

Cell communication and signaling : CCS 20240117 1

Adenosine-to-inosine (A-to-I) editing of RNA, catalyzed by adenosine deaminase acting on RNA (ADAR) enzymes, is a prevalent RNA modification in mammals. It has been shown that A-to-I editing plays a critical role in multiple diseases, such as cardiovascular disease, neurological disorder, and particularly cancer. ADARs are the family of enzymes, including ADAR1, ADAR2, and ADAR3, that catalyze the occurrence of A-to-I editing. Notably, A-to-I editing is mainly catalyzed by ADAR1. Given the signi ...[more]

PMID: 38233935

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ADAR1-Mediated RNA Editing and Its Role in Cancer.

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The ADAR1 editome reveals drivers of editing-specificity for ADAR1-isoforms.

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A-to-I editing of Malacoherpesviridae RNAs supports the antiviral role of ADAR1 in mollusks.

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ADAR1-mediated RNA editing promotes B cell lymphomagenesis.

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Dimerization of ADAR1 modulates site-specificity of RNA editing.

Project description:Adenosine-to-inosine editing is catalyzed by adenosine deaminases acting on RNA (ADARs) in double-stranded RNA (dsRNA) regions. Although three ADARs exist in mammals, ADAR1 is responsible for the vast majority of the editing events and acts on thousands of sites in the human transcriptome. ADAR1 has been proposed to form a stable homodimer and dimerization is suggested to be important for editing activity. In the absence of a structural basis for the dimerization of ADAR1, and without a way to prevent dimer formation, the effect of dimerization on enzyme activity or site specificity has remained elusive. Here, we report on the structural analysis of the third double-stranded RNA-binding domain of ADAR1 (dsRBD3), which reveals stable dimer formation through a large inter-domain interface. Exploiting these structural insights, we engineered an interface-mutant disrupting ADAR1-dsRBD3 dimerization. Notably, dimerization disruption did not abrogate ADAR1 editing activity but intricately affected editing efficiency at selected sites. This suggests a complex role for dimerization in the selection of editing sites by ADARs, and makes dimerization a potential target for modulating ADAR1 editing activity.

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