ArticleNucleic acids research2022
ADAR activation by inducing a syn conformation at guanosine adjacent to an editing site.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 32 citations in OpenAlex.
- Structure-aware graph learning predicts RNA editability across tissues and species.Research square · 2026Article
- Improved RNA base editing with guide RNAs mimicking highly edited endogenous ADAR substrates.Nature biotechnology · 2026Article
- Synthesis of 2'-O,4'-Cα-Dimethyl Ribonucleoside Analogs and Their Effects on RNA and Modulation of ADAR Editing.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- Discovery and Tuning of RNA Editing Guides via High-Throughput Screening and Chemical Modification.Chembiochem : a European journal of chemical biology · 2025Article
- Evaluation of in vitro liver models and non-human primates for predicting ADAR RNA editing efficiency in human liver.Scientific reports · 2025Article
- Control of ADAR2 Dimerization and RNA Editing Efficiency by Site-Specific 2'-Fluoro Modification of Guide RNAs.ACS chemical biology · 2025Article
- Exploring the complexity of MECP2 function in Rett syndrome.Nature reviews. Neuroscience · 2025Review
- A systematic evaluation of the therapeutic potential of endogenous-ADAR editors in cancer prevention and treatment.NAR cancer · 2025Article
- Phylogenetic and structural analysis of Hydra ADAR.Archives of biochemistry and biophysics · 2025Article
- Cooperative role of PACT and ADAR1 in preventing aberrant PKR activation by self-derived double-stranded RNA.Nature communications · 2025Article
- Spontaneous base flipping helps drive Nsp15's preferences in double stranded RNA substrates.Nature communications · 2025Article
- En masse evaluation of RNA guides (EMERGe) for ADARs.Methods in enzymology · 2025Article
- Structural analysis of human ADAR2-RNA complexes by X-ray crystallography.Methods in enzymology · 2025Article
- Nucleoside Analogs in ADAR Guide Strands Enable Editing at 5'-GBiomolecules · 2024Article
- Rational design of base, sugar and backbone modifications improves ADAR-mediated RNA editing.Nucleic acids research · 2024Article
- Structural perspectives on adenosine to inosine RNA editing by ADARs.Molecular therapy. Nucleic acids · 2024Review
- Structural and functional effects of inosine modification in mRNA.RNA (New York, N.Y.) · 2024Article
- RNA sequences that direct selective ADAR editing from a SELEX library bearing 8-azanebularine.Bioorganic & medicinal chemistry · 2024Article
- RNA editing enzymes: structure, biological functions and applications.Cell & bioscience · 2024Review
- A pipeline for identifying guide RNA sequences that promote RNA editing of nonsense mutations that cause inherited retinal diseases.Molecular therapy. Nucleic acids · 2024Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
ADARs (adenosine deaminases acting on RNA) can be directed to sites in the transcriptome by complementary guide strands allowing for the correction of disease-causing mutations at the RNA level. However, ADARs show bias against editing adenosines with a guanosine 5' nearest neighbor (5'-GA sites), limiting the scope of this approach. Earlier studies suggested this effect arises from a clash in the RNA minor groove involving the 2-amino group of the guanosine adjacent to an editing site. Here we show that nucleosides capable of pairing with guanosine in a syn conformation enhance editing for 5'-GA sites. We describe the crystal structure of a fragment of human ADAR2 bound to RNA bearing a G:G pair adjacent to an editing site. The two guanosines form a Gsyn:Ganti pair solving the steric problem by flipping the 2-amino group of the guanosine adjacent to the editing site into the major groove. Also, duplexes with 2'-deoxyadenosine and 3-deaza-2'-deoxyadenosine displayed increased editing efficiency, suggesting the formation of a Gsyn:AH+anti pair. This was supported by X-ray crystallography of an ADAR complex with RNA bearing a G:3-deaza dA pair. This study shows how non-Watson-Crick pairing in duplex RNA can facilitate ADAR editing enabling the design of next generation guide strands for therapeutic RNA editing.
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