{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["620(7974)"],"submitter":["Saito M"],"pubmed_abstract":["RNA-guided systems, which use complementarity between a guide RNA and target nucleic acid sequences for recognition of genetic elements, have a central role in biological processes in both prokaryotes and eukaryotes. For example, the prokaryotic CRISPR-Cas systems provide adaptive immunity for bacteria and archaea against foreign genetic elements. Cas effectors such as Cas9 and Cas12 perform guide-RNA-dependent DNA cleavage<sup>1</sup>. Although a few eukaryotic RNA-guided systems have been studied, including RNA interference<sup>2</sup> and ribosomal RNA modification<sup>3</sup>, it remains unclear whether eukaryotes have RNA-guided endonucleases. Recently, a new class of prokaryotic RNA-guided systems (termed OMEGA) was reported<sup>4,5</sup>. The OMEGA effector TnpB is the putative ancestor of Cas12 and has RNA-guided endonuclease activity<sup>4,6</sup>. TnpB may also be the ancestor of the eukaryotic transposon-encoded Fanzor (Fz) proteins<sup>4,7</sup>, raising the possibility that eukaryotes are also equipped with CRISPR-Cas or OMEGA-like programmable RNA-guided endonucleases. Here we report the biochemical characterization of Fz, showing that it is an RNA-guided DNA endonuclease. We also show that Fz can be reprogrammed for human genome engineering applications. Finally, we resolve the structure of Spizellomyces punctatus Fz at 2.7 Å using cryogenic electron microscopy, showing the conservation of core regions among Fz, TnpB and Cas12, despite diverse cognate RNA structures. Our results show that Fz is a eukaryotic OMEGA system, demonstrating that RNA-guided endonucleases are present in all three domains of life."],"journal":["Nature"],"pagination":["660-668"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10432273"],"repository":["biostudies-literature"],"pubmed_title":["Fanzor is a eukaryotic programmable RNA-guided endonuclease."],"pmcid":["PMC10432273"],"pubmed_authors":["Maguire S","Zhang F","Kannan S","Xu P","Faure G","Vo S","Altae-Tran H","Desimone A","Saito M","Macrae RK"],"additional_accession":[]},"is_claimable":false,"name":"Fanzor is a eukaryotic programmable RNA-guided endonuclease.","description":"RNA-guided systems, which use complementarity between a guide RNA and target nucleic acid sequences for recognition of genetic elements, have a central role in biological processes in both prokaryotes and eukaryotes. For example, the prokaryotic CRISPR-Cas systems provide adaptive immunity for bacteria and archaea against foreign genetic elements. Cas effectors such as Cas9 and Cas12 perform guide-RNA-dependent DNA cleavage<sup>1</sup>. Although a few eukaryotic RNA-guided systems have been studied, including RNA interference<sup>2</sup> and ribosomal RNA modification<sup>3</sup>, it remains unclear whether eukaryotes have RNA-guided endonucleases. Recently, a new class of prokaryotic RNA-guided systems (termed OMEGA) was reported<sup>4,5</sup>. The OMEGA effector TnpB is the putative ancestor of Cas12 and has RNA-guided endonuclease activity<sup>4,6</sup>. TnpB may also be the ancestor of the eukaryotic transposon-encoded Fanzor (Fz) proteins<sup>4,7</sup>, raising the possibility that eukaryotes are also equipped with CRISPR-Cas or OMEGA-like programmable RNA-guided endonucleases. Here we report the biochemical characterization of Fz, showing that it is an RNA-guided DNA endonuclease. We also show that Fz can be reprogrammed for human genome engineering applications. Finally, we resolve the structure of Spizellomyces punctatus Fz at 2.7 Å using cryogenic electron microscopy, showing the conservation of core regions among Fz, TnpB and Cas12, despite diverse cognate RNA structures. Our results show that Fz is a eukaryotic OMEGA system, demonstrating that RNA-guided endonucleases are present in all three domains of life.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Aug","modification":"2024-11-13T19:10:13.618Z","creation":"2024-11-13T19:10:13.618Z"},"accession":"S-EPMC10432273","cross_references":{"pubmed":["37380027"],"doi":["10.1038/s41586-023-06356-2"]}}