TIGR-Tas: A family of modular RNA-guided DNA-targeting systems in prokaryotes and their viruses.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40014690.
- Also identified by DOI 10.1126/science.adv9789 and PMC identifier 12045711.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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.
Medical subject headings
- Bacterial Proteins
- Bacteriophages
- CRISPR-Cas Systems
- RNA, Guide, CRISPR-Cas Systems
- Clustered Regularly Interspaced Short Palindromic Repeats
- Eubacteriales
- Gene Editing