To protect and modify double-stranded RNA – the critical roles of ADARs in development, immunity and oncogenesis

Erdmann, Emily; Mahapatra, A. P. K.; Mukherjee, Priyanka; Yang, Boyoon; Hundley, Heather A.

doi:10.1080/10409238.2020.1856768

Cited by 33 publications

(31 citation statements)

References 252 publications

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“…The adenosine deaminase acting on RNA (ADAR) enzymes convert adenosine to inosine in double-stranded (ds)RNA(as reviewed in (Heraud-Farlow and Walkley 2020;Erdmann et al 2021)). In recent years ADAR1, which is one of the two enzymatically active members of the ADAR family in mammals, has received the lion's-share of attention (as reviewed in (Quin et al 2021;Baker and Slack 2022;Song et al 2022)).…”

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confidence: 99%

ADAR2 enzymes: efficient site-specific RNA editors with gene therapy aspirations

Hajji

Sedmik

Cherian

et al. 2022

RNA

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The adenosine deaminase acting on RNA (ADAR) enzymes are essential for neuronal function and innate immune control. ADAR1 RNA editing prevents aberrant activation of antiviral dsRNA sensors, through editing of long double-stranded RNAs (dsRNAs). In this review we focus on the ADAR2 proteins involved in the efficient, highly site-specific RNA editing to recode open reading frames first discovered in the GRIA2 transcript encoding the key GLUA2 subunit of AMPA receptors; ADAR1 proteins also edits many sites. We summarize the history of ADAR2 protein research and give an up to date review of ADAR2 structural studies, human ADARBI(ADAR2) mutants causing severe infant seizures and mouse disease models. Structural studies on ADARs and their RNA substrates facilitate current efforts to develop ADAR RNA editing gene therapy to edit disease-causing single nucleotide polymorphisms (SNPs). Artificial ADAR guide RNAs are being developed to retarget ADAR RNA editing to new target transcripts in order to correct SNP mutations in them at the RNA level. Site-specific RNA editing has been expanded to recode hundreds of sites in CNS transcripts in Drosophila and cephalopods. In Drosophila and C. elegans ADAR RNA editing also suppresses responses to self dsRNA.

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confidence: 99%

ADAR2 enzymes: efficient site-specific RNA editors with gene therapy aspirations

Hajji

Sedmik

Cherian

et al. 2022

RNA

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“…A striking characteristic of the 3,316 identified ADAR3-bound target RNAs is that nearly 80% (2,611) are present in REDIportal (41), a database of A-to-I editing events (Supplementary Table 1a). We previously demonstrated that, in U87 cells, ADAR3 binding to one transcript, GRIA2, was important for the ability of ADAR3 to inhibit editing at the Q/R site, which is an essential editing event catalyzed by ADAR2 (42).…”

Section: Adar3 Inhibits Rna Editing Across the Transcriptomementioning

confidence: 99%

RNA binding by ADAR3 inhibits adenosine-to-inosine editing and promotes expression of immune response protein MAVS

Kurup¹,

Oakes²,

Manning³

et al. 2022

Journal of Biological Chemistry

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“…In glioblastoma, ADAR3 has been reported to be upregulated to competitively inhibit RNA editing at the Q/R site of GRIA2 by ADAR2 ( Oakes et al, 2017 ; Wang et al, 2018 ). And these genes of the ADAR family have similar domain structures, mainly composed of a deaminase domain and two or three dsRNA binding domains (dsRBDs) ( Erdmann et al, 2021 ; Quin et al, 2021 ). The deaminase domain of both ADAR1 and ADAR2 catalyzes the hydrolytic deamination of adenosine to inosine in dsRNA, while the catalytic activity of ADAR3 has not been reported so far ( Chen et al, 2000 ; Nishikura, 2016 ; Oakes et al, 2017 ; Samuel, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

ADAR1-Mediated RNA Editing and Its Role in Cancer

Liu

Wang

Zhang

et al. 2022

Front. Cell Dev. Biol.

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It is well known that the stability of RNA, the interaction between RNA and protein, and the correct translation of protein are significant forces that drive the transition from normal cell to malignant tumor. Adenosine deaminase acting on RNA 1 (ADAR1) is an RNA editing enzyme that catalyzes the deamination of adenosine to inosine (A-to-I), which is one dynamic modification that in a combinatorial manner can give rise to a very diverse transcriptome. ADAR1-mediated RNA editing is essential for survival in mammals and its dysregulation results in aberrant editing of its substrates that may affect the phenotypic changes in cancer. This overediting phenomenon occurs in many cancers, such as liver, lung, breast, and esophageal cancers, and promotes tumor progression in most cases. In addition to its editing role, ADAR1 can also play an editing-independent role, although current research on this mechanism is relatively shallowly explored in tumors. In this review, we summarize the nature of ADAR1, mechanisms of ADAR1 editing-dependent and editing-independent and implications for tumorigenesis and prognosis, and pay special attention to effects of ADAR1 on cancers by regulating non-coding RNA formation and function.

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To protect and modify double-stranded RNA – the critical roles of ADARs in development, immunity and oncogenesis

Cited by 33 publications

References 252 publications

ADAR2 enzymes: efficient site-specific RNA editors with gene therapy aspirations

ADAR2 enzymes: efficient site-specific RNA editors with gene therapy aspirations

RNA binding by ADAR3 inhibits adenosine-to-inosine editing and promotes expression of immune response protein MAVS

ADAR1-Mediated RNA Editing and Its Role in Cancer

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