The widespread IS200/IS605 transposon family encodes diverse programmable RNA-guided endonucleases.
basic_science · Level V
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- Record sourced from PubMed, PMID 34591643.
- Also identified by DOI 10.1126/science.abj6856 and PMC identifier 8929163.
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Abstract
IscB proteins are putative nucleases encoded in a distinct family of IS200/IS605 transposons and are likely ancestors of the RNA-guided endonuclease Cas9, but the functions of IscB and its interactions with any RNA remain uncharacterized. Using evolutionary analysis, RNA sequencing, and biochemical experiments, we reconstructed the evolution of CRISPR-Cas9 systems from IS200/IS605 transposons. We found that IscB uses a single noncoding RNA for RNA-guided cleavage of double-stranded DNA and can be harnessed for genome editing in human cells. We also demonstrate the RNA-guided nuclease activity of TnpB, another IS200/IS605 transposon-encoded protein and the likely ancestor of Cas12 endonucleases. This work reveals a widespread class of transposon-encoded RNA-guided nucleases, which we name OMEGA (obligate mobile element–guided activity), with strong potential for developing as biotechnologies.
Medical subject headings
- Bacterial Proteins
- CRISPR-Associated Protein 9
- CRISPR-Associated Proteins
- CRISPR-Cas Systems
- DNA Transposable Elements
- Endodeoxyribonucleases
- Evolution, Molecular
- RNA, Guide, CRISPR-Cas Systems