Program > Browse abstracts by author > Macrae Rhiannon K.

Over the past decade, the fascination with programmable RNA-guided DNA nucleases, primarily found in prokaryotes, continues to drive research exploration. Recent discoveries have unveiled a new class of prokaryotic RNA-guided systems known as OMEGA, with the effector TnpB identified as the putative ancestor of Cas12, exhibiting RNA-guided endonuclease activity. Intriguingly, TnpB also appears to share ancestry with eukaryotic transposon-encoded Fanzor proteins, suggesting the potential presence of OMEGA-like programmable RNA-guided endonucleases in eukaryotes. In this study, employing biochemical and molecular biology approaches, we showed that Fanzor proteins use non-coding RNA as a guide to target DNA precisely, and that they can be reprogrammed to edit the genome of human cells. Moreover, the structure of Spizellomyces punctatus Fanzor highlighted the conservation of core regions among Fanzor, TnpB, and Cas12, confirming that Fanzors is a eukaryotic OMEGA system. These results underscored the ubiquitous presence of RNA-guided endonucleases in all three domains of life.