Researchers seeking to understand the origins of CRISPR-Cas9 systems have uncovered a class of transposon-encoded RNA-guided nucleases, which they dubbed "OMEGA," that could be harnessed for genome editing in human cells. These systems hold strong potential for developing as biotechnologies, the authors say.
CRISPR-Cas systems have transformed genome editing and other biotechnologies; however the broader origins and diversity of these RNA-guided mechanisms have largely remained unexplored. The likely ancestors of the RNA-guided endonuclease Cas9 are a group of proteins – IscB proteins – in a family of transposons known as the IS200/IS605 transposons.
Here, Han Altae-Tran and Feng Zhang and colleagues reconstructed the evolution of CRISPR-Cas9 systems from IS200/IS605 transposons. In doing so, they report that three distinct transposon-encoded proteins, IscB, IsrB, and TnpB, are naturally occurring, reprogrammable, RNA-guided DNA nucleases that can be harnessed for genome editing in human cells. The authors dubbed these newly characterized systems OMEGA (Obligate Mobile Element Guided Activity).
"The broad distribution of the…systems characterized here indicates that RNA-guided mechanisms are more widespread in prokaryotes than previously suspected," they say, "and suggests that RNA-guided activities are likely ancient and evolved on multiple, independent occasions, of which only the most common ones have likely been identified so far."
Altae-Trant, H., et al. (2021) The widespread IS200/605 transposon family encodes diverse programmable RNA-guided endonucleases. Science. doi.org/10.1126/science.abj6856.