Structure-guided discovery of ancestral CRISPR-Cas13 ribonucleases.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39024377.
- Also identified by DOI 10.1126/science.adq0553 and PMC identifier 12165695.
- No licence information is recorded for this record.
- Because redistribution is not established, this page shows the abstract only. Follow the links below for the full text.
Abstract
The RNA-guided ribonuclease CRISPR-Cas13 enables adaptive immunity in bacteria and programmable RNA manipulation in heterologous systems. Cas13s share limited sequence similarity, hindering discovery of related or ancestral systems. To address this, we developed an automated structural-search pipeline to identify an ancestral clade of Cas13 (Cas13an) and further trace Cas13 origins to defense-associated ribonucleases. Despite being one-third the size of other Cas13s, Cas13an mediates robust programmable RNA depletion and defense against diverse bacteriophages. However, unlike its larger counterparts, Cas13an uses a single active site for both CRISPR RNA processing and RNA-guided cleavage, revealing that the ancestral nuclease domain has two modes of activity. Discovery of Cas13an deepens our understanding of CRISPR-Cas evolution and expands opportunities for precision RNA editing, showcasing the promise of structure-guided genome mining.
Medical subject headings
- CRISPR-Associated Proteins
- CRISPR-Cas Systems
- Evolution, Molecular
- Ribonucleases
- RNA Editing
- RNA, Guide, CRISPR-Cas Systems