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[Preprint]. 2023 Aug 10:2023.08.09.552727.
doi: 10.1101/2023.08.09.552727.

Eukaryotic RNA-guided endonucleases evolved from a unique clade of bacterial enzymes

Peter H Yoon, Petr Skopintsev, Honglue Shi, Lin-Xing Chen, Benjamin A Adler, Muntathar Al-Shimary, Rory J Craig, Zheng Li, Jasmine Amerasekera, Marena Trinidad, Hunter Nisonoff, Kai Chen, Arushi Lahiri, Ron Boger, Steve Jacobsen, Jillian F Banfield, Jennifer A Doudna

Eukaryotic RNA-guided endonucleases evolved from a unique clade of bacterial enzymes

Peter H Yoon et al. bioRxiv. .

Update in

  • Eukaryotic RNA-guided endonucleases evolved from a unique clade of bacterial enzymes.
    Yoon PH, Skopintsev P, Shi H, Chen L, Adler BA, Al-Shimary M, Craig RJ, Loi KJ, DeTurk EC, Li Z, Amerasekera J, Trinidad M, Nisonoff H, Chen K, Lahiri A, Boger R, Jacobsen S, Banfield JF, Doudna JA. Yoon PH, et al. Nucleic Acids Res. 2023 Dec 11;51(22):12414-12427. doi: 10.1093/nar/gkad1053. Nucleic Acids Res. 2023. PMID: 37971304 Free PMC article.

Abstract

RNA-guided endonucleases form the crux of diverse biological processes and technologies, including adaptive immunity, transposition, and genome editing. Some of these enzymes are components of insertion sequences (IS) in the IS200/IS605 and IS607 transposon families. Both IS families encode a TnpA transposase and TnpB nuclease, an RNA-guided enzyme ancestral to CRISPR-Cas12. In eukaryotes and their viruses, TnpB homologs occur as two distinct types, Fanzor1 and Fanzor2. We analyzed the evolutionary relationships between prokaryotic TnpBs and eukaryotic Fanzors, revealing that a clade of IS607 TnpBs with unusual active site arrangement found primarily in Cyanobacteriota likely gave rise to both types of Fanzors. The wide-spread nature of Fanzors imply that the properties of this particular group of IS607 TnpBs were particularly suited to adaptation and evolution in eukaryotes and their viruses. Experimental characterization of a prokaryotic IS607 TnpB and virally encoded Fanzor1s uncovered features that may have fostered coevolution between TnpBs/Fanzors and their cognate transposases. Our results provide insight into the evolutionary origins of a ubiquitous family of RNA-guided proteins that shows remarkable conservation across domains of life.

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