ArticleNucleic acids research2016
Probing RNA recognition by human ADAR2 using a high-throughput mutagenesis method.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 34 citations in OpenAlex.
- Evolution of Engineered ADAR-Based RNA Editing Systems.International journal of molecular sciences · 2026Review
- A pipeline for identifying guide RNA sequences that promote RNA editing of nonsense mutations that cause inherited retinal diseases.Molecular therapy. Nucleic acids · 2024Article
- In Silico Discovery of Potential Inhibitors Targeting the RNA Binding Loop of ADAR2 and 5-HT2CR from Traditional Chinese Natural Compounds.International journal of molecular sciences · 2023Article
- Molecular Docking and Dynamics Simulation Studies Predict Potential Anti-ADAR2 Inhibitors: Implications for the Treatment of Cancer, Neurological, Immunological and Infectious Diseases.International journal of molecular sciences · 2023Article
- Identification of exceptionally potent adenosine deaminases RNA editors from high body temperature organisms.PLoS genetics · 2023Article
- ADAR2 enzymes: efficient site-specific RNA editors with gene therapy aspirations.RNA (New York, N.Y.) · 2022Review
- Article
- High-throughput mutagenesis reveals unique structural features of human ADAR1.Nature communications · 2020Article
- RNA binding candidates for human ADAR3 from substrates of a gain of function mutant expressed in neuronal cells.Nucleic acids research · 2019Article
- A cytosine deaminase for programmable single-base RNA editing.Science (New York, N.Y.) · 2019Article
- Sensitive ADAR editing reporter in cancer cells enables high-throughput screening of small molecule libraries.Nucleic acids research · 2019Article
- A Bump-Hole Approach for Directed RNA Editing.Cell chemical biology · 2019Article
- Selective Recognition of RNA Substrates by ADAR Deaminase Domains.Biochemistry · 2018Article
- Site-directed RNA repair of endogenous Mecp2 RNA in neurons.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- How do ADARs bind RNA? New protein-RNA structures illuminate substrate recognition by the RNA editing ADARs.BioEssays : news and reviews in molecular, cellular and developmental biology · 2017Review
- Revealing the hidden RBP-RNA interactions with RNA modification enzyme-based strategies.Wiley interdisciplinary reviews. RNAReview
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Adenosine deamination is one of the most prevalent post-transcriptional modifications in mRNA. In humans, ADAR1 and ADAR2 catalyze this modification and their malfunction correlates with disease. Recently our laboratory reported crystal structures of the human ADAR2 deaminase domain bound to duplex RNA revealing a protein loop that binds the RNA on the 5' side of the modification site. This 5' binding loop appears to be one contributor to substrate specificity differences between ADAR family members. In this study, we endeavored to reveal detailed structure-activity relationships in this loop to advance our understanding of RNA recognition by ADAR2. To achieve this goal, we established a high-throughput mutagenesis approach which allows rapid screening of ADAR variants in single yeast cells and provides quantitative evaluation for enzymatic activity. Using this approach, we determined the importance of specific amino acids at 19 different positions in the ADAR2 5' binding loop and revealed six residues that provide essential structural elements supporting the fold of the loop and key RNA-binding functional groups. This work provided new insight into RNA recognition by ADAR2 and established a new tool for defining structure-function relationships in ADAR reactions.
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