| Literature DB >> 34591643 |
Han Altae-Tran1,2,3,4,5, Soumya Kannan1,2,3,4,5, F Esra Demircioglu1,2,3,4,5, Rachel Oshiro1,2,3,4,5, Suchita P Nety1,2,3,4,5, Luke J McKay6,7,8, Mensur Dlakić9, William P Inskeep6,7, Kira S Makarova10, Rhiannon K Macrae1,2,3,4,5, Eugene V Koonin10, Feng Zhang1,2,3,4,5.
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.Entities:
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Year: 2021 PMID： 34591643 PMCID： PMC8929163 DOI： 10.1126/science.abj6856
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728