ArticleCell research2024
Discovery and structural mechanism of DNA endonucleases guided by RAGATH-18-derived RNAs.
Article in Cell research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 10 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
10 citing papers in PubMed.
- Review
- Identification of 3D motifs in Rfam with JAR3D.RNA (New York, N.Y.) · 2026Article
- An anti-CRISPR targets the sgRNA to block Cas9 and guides the design of enhanced genome editors.Nature structural & molecular biology · 2026Article
- Comprehensive assessment of activity, specificity, and safety of hypercompact TnpB systems for gene editing.Genome biology · 2026Article
- Enhanced SfaTnpB enables single-base-specific, one-pot nucleic acid detection for high-sensitivity diagnostics.Nucleic acids research · 2026Article
- Engineering TnpB as a compact RNA-guided genome editor from molecular constraints to design principles.Frontiers in genome editing · 2026Review
- Genomic epidemiology and the evolution ofMicrobial genomics · 2025Article
- Functions and mechanisms of eukaryotic RNA-guided programmed DNA elimination.Biochemical Society transactions · 2025Review
- Characterization of the genome editing with miniature DNA nucleases TnpB and IscB in Escherichia coli strains.Communications biology · 2025Article
- Review
Corrections and comments
- Erratum issued
Authors and funding
13 authors.
Funding
Abstract
CRISPR-Cas systems and IS200/IS605 transposon-associated TnpBs have been utilized for the development of genome editing technologies. Using bioinformatics analysis and biochemical experiments, here we present a new family of RNA-guided DNA endonucleases. Our bioinformatics analysis initially identifies the stable co-occurrence of conserved RAGATH-18-derived RNAs (reRNAs) and their upstream IS607 TnpBs with an average length of 390 amino acids. IS607 TnpBs form programmable DNases through interaction with reRNAs. We discover the robust dsDNA interference activity of IS607 TnpB systems in bacteria and human cells. Further characterization of the Firmicutes bacteria IS607 TnpB system (ISFba1 TnpB) reveals that its dsDNA cleavage activity is remarkably sensitive to single mismatches between the guide and target sequences in human cells. Our findings demonstrate that a length of 20 nt in the guide sequence of reRNA achieves the highest DNA cleavage activity for ISFba1 TnpB. A cryo-EM structure of the ISFba1 TnpB effector protein bound by its cognate RAGATH-18 motif-containing reRNA and a dsDNA target reveals the mechanisms underlying reRNA recognition by ISFba1 TnpB, reRNA-guided dsDNA targeting, and the sensitivity of the ISFba1 TnpB system to base mismatches between the guide and target DNA. Collectively, this study identifies the IS607 TnpB family of compact and specific RNA-guided DNases with great potential for application in gene editing.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.