Adenosine Deaminases That Act on RNA (ADARs)

Wang, Yuru; Zheng, Yuxuan; Beal, Peter A.

doi:10.1016/bs.enz.2017.03.006

Cited by 38 publications

(46 citation statements)

References 256 publications

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“…These enzymes deaminate the adenine base to hypoxanthine, resulting in an I instead of an A nucleotide. ADARs contain a deaminase domain and dsRNA-binding domains that bind to double-stranded RNA regions in which the editing sites are located [ 17 ]. Besides RNA secondary structure, the base opposite to the target A (preferentially a C) and the flanking nucleotides affect editing efficiency.…”

Section: Q3: How Is Rna Editing Catalyzed?mentioning

confidence: 99%

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Adenosine to inosine mRNA editing in fungi and how it may relate to fungal pathogenesis

Teichert

2018

PLoS Pathog

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Section: Q3: How Is Rna Editing Catalyzed?mentioning

confidence: 99%

“…Fungi, like plants, do not encode ADAR homologs, and it remains unknown how fungi catalyze A-to-I RNA editing [ 9 , 17 ]. Fungal editing, in contrast to metazoan editing, preferentially targets As in hairpin loops, and loop stability affects editing efficiency [ 11 ].…”

Section: Q3: How Is Rna Editing Catalyzed?mentioning

confidence: 99%

Adenosine to inosine mRNA editing in fungi and how it may relate to fungal pathogenesis

Teichert

2018

PLoS Pathog

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“…Here, we will discuss the pioneering studies starting to build a molecular foundation basis for understanding the epitranscriptome. We will focus on studies of modifications other than inosine, as adenosine to inosine (A to I) editing has been extensively reviewed elsewhere (Nishikura, ; Walkley & Li, ; Y. Wang, Zheng, & Beal, ). This review will emphasize the work conducted to quantify modification abundance, frequency of incorporation, and interactions with the cellular machinery.…”

Section: Introductionmentioning

confidence: 99%

A molecular‐level perspective on the frequency, distribution, and consequences of messenger RNA modifications

2020

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Cells use chemical modifications to alter the sterics, charge, and conformations of large biomolecules, modulating their biogenesis, function, and stability. Until recently post‐transcriptional RNA modifications were thought to be largely limited to nonprotein coding RNA species. However, this dogma has rapidly transformed with the discovery of a host of modifications in protein coding messenger RNAs (mRNAs). Recent advancements in genome‐wide sequencing technologies have enabled the identification of mRNA modifications as a potential new frontier in gene regulation—leading to the development of the epitranscriptome field. As a result, there has been a flurry of multiple groundbreaking discoveries, including new modifications, nucleoside modifying enzymes (“writers” and “erasers”), and RNA binding proteins that recognize chemical modifications (“readers”). These discoveries opened the door to understanding how post‐transcriptional mRNA modifications can modulate the mRNA lifecycle, and established a link between the epitranscriptome and human health and disease. Despite a rapidly growing recognition of their importance, fundamental questions regarding the identity, prevalence, and functional consequences of mRNA modifications remain to be answered. Here, we highlight quantitative studies that characterize mRNA modification abundance, frequency, and interactions with cellular machinery. As the field progresses, we see a need for the further integration of quantitative and reductionist approaches to complement transcriptome wide studies in order to establish a molecular‐level framework for understanding the consequences of mRNA chemical modifications on biological processes. This article is categorized under: RNA Structure and Dynamics > RNA Structure, Dynamics and Chemistry RNA Processing > RNA Editing and Modification

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“…RNA editing is an important mechanism that greatly diversifies the transcriptome and proteome in higher eukaryotes [1][2][3][4][5] . In animals, the predominant type of RNA editing is the hydrolytic deamination of adenosine (A) to form inosine (I), catalyzed by adenosine deaminase acting on RNA (ADAR) 6,7 .…”

Section: Introductionmentioning

confidence: 99%

Learning cis-regulatory principles of ADAR-based RNA editing from CRISPR-mediated mutagenesis

Liu

Sun

Shcherbina

et al. 2019

Preprint

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Adenosine-to-inosine (A-to-I) RNA editing catalyzed by ADAR enzymes occurs in double-stranded RNAs (dsRNAs). How the RNA sequence and structure (i.e., the cis-regulation) determine the editing efficiency and specificity is poorly understood, despite a compelling need towards functional understanding of known editing events and transcriptome engineering of desired adenosines. We developed a CRISPR/Cas9-mediated saturation mutagenesis approach to generate comprehensive libraries of point mutations near an editing site and its editing complementary sequence (ECS) at the endogenous genomic locus. We used machine learning to integrate diverse RNA sequence features and computationally predicted structures to model editing levels measured by deep sequencing and identified cis-regulatory features of RNA editing. As proof-of-concept, we applied this integrative approach to three editing substrates. Our models explained over 70% of variation in editing levels. The models indicate that RNA sequence and structure features synergistically determine the editing levels.Our integrative approach can be broadly applied to any editing site towards the goal of deciphering the RNA editing code. It also provides guidance for designing and screening of antisense RNA sequences that form dsRNA duplex with the target transcript for ADAR-mediated transcriptome engineering.

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Adenosine Deaminases That Act on RNA (ADARs)

Cited by 38 publications

References 256 publications

Adenosine to inosine mRNA editing in fungi and how it may relate to fungal pathogenesis

Adenosine to inosine mRNA editing in fungi and how it may relate to fungal pathogenesis

A molecular‐level perspective on the frequency, distribution, and consequences of messenger RNA modifications

Learning cis-regulatory principles of ADAR-based RNA editing from CRISPR-mediated mutagenesis

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