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-seq, and biochemical experiments, we
reconstruct the evolution of CRISPR-Cas9 systems from IS200/IS605
transposons.

We show that IscB utilizes a single non-coding 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
IS200/605 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

The widespread IS200/605 transposon family encodes diverse programmable
RNA-guided endonucleases (science.org)
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