The widespread IS200/IS605 transposon family encodes diverse programmable RNA-guided endonucleases
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nihms-1751823.pdf
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Accepted version
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2.09 MB
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Author(s)
Altae-Tran, Han
Kannan, Soumya
Demircioglu, F Esra
Oshiro, Rachel
Nety, Suchita P
McKay, Luke J
Dlakić, Mensur
Inskeep, William P
Makarova, Kira S
Macrae, Rhiannon K
Date Issued
October 2021
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Altae-Tran, Han, Kannan, Soumya, Demircioglu, F Esra, Oshiro, Rachel, Nety, Suchita P et al. 2021. "The widespread IS200/IS605 transposon family encodes diverse programmable RNA-guided endonucleases." Science, 374 (6563).
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Author's final manuscript
Abstract
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 sequencing, and biochemical experiments, we reconstructed the evolution of CRISPR-Cas9 systems from IS200/IS605 transposons. We found that IscB uses a single noncoding 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/IS605 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.
MIT Department
Howard Hughes Medical Institute
McGovern Institute for Brain Research at MIT
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Massachusetts Institute of Technology. Department of Biological Engineering
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DOI of Published Version
https://doi.org/10.1126/science.abj6856
