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TitleTIGR-Tas: A family of modular RNA-guided DNA-targeting systems in prokaryotes and their viruses.
Journal, issue, pagesScience, Vol. 388, Issue 6746, Page eadv9789, Year 2025
Publish dateMay 1, 2025
AuthorsGuilhem Faure / Makoto Saito / Max E Wilkinson / Natalia Quinones-Olvera / Peiyu Xu / Daniel Flam-Shepherd / Stephanie Kim / Nishith Reddy / Shiyou Zhu / Lilia Evgeniou / Eugene V Koonin / Rhiannon K Macrae / Feng Zhang /
PubMed AbstractRNA-guided systems provide remarkable versatility, enabling diverse biological functions. Through iterative structural and sequence homology-based mining starting with a guide RNA-interaction domain ...RNA-guided systems provide remarkable versatility, enabling diverse biological functions. Through iterative structural and sequence homology-based mining starting with a guide RNA-interaction domain of Cas9, we identified a family of RNA-guided DNA-targeting proteins in phage and parasitic bacteria. Each system consists of a tandem interspaced guide RNA (TIGR) array and a TIGR-associated (Tas) protein containing a nucleolar protein (Nop) domain, sometimes fused to HNH (TasH)- or RuvC (TasR)-nuclease domains. We show that TIGR arrays are processed into 36-nucleotide RNAs (tigRNAs) that direct sequence-specific DNA binding through a tandem-spacer targeting mechanism. TasR can be reprogrammed for precise DNA cleavage, including in human cells. The structure of TasR reveals striking similarities to box C/D small nucleolar ribonucleoproteins and IS110 RNA-guided transposases, providing insights into the evolution of diverse RNA-guided systems.
External linksScience / PubMed:40014690 / PubMed Central
MethodsEM (single particle)
Resolution3.05 Å
Structure data

EMDB-48616, PDB-9mty:
Structure of TIGR-TasR in complex with tigRNA and target DNA after DNA cleavage
Method: EM (single particle) / Resolution: 3.05 Å

Chemicals

ChemComp-MG:
Unknown entry

Source
  • thermoproteota archaeon (archaea)
  • escherichia coli (E. coli)
KeywordsDNA BINDING PROTEIN/RNA/DNA / nuclease / RNA-guided / Nop domain / DNA-binding protein / DNA-RNA HYBRID / DNA BINDING PROTEIN-RNA-DNA complex

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