The widespread IS200/IS605 transposon family encodes diverse programmable RNA-guided endonucleases
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Association for the Advancement of Science (AAAS)
2022
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| Online Access: | https://hdl.handle.net/1721.1/142061 |
| _version_ | 1826207196562587648 |
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| author | 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 Koonin, Eugene V Zhang, Feng |
| author2 | Howard Hughes Medical Institute |
| author_facet | Howard Hughes Medical Institute 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 Koonin, Eugene V Zhang, Feng |
| author_sort | Altae-Tran, Han |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T13:45:34Z |
| format | Article |
| id | mit-1721.1/142061 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T13:45:34Z |
| publishDate | 2022 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/1420612023-04-10T19:04:12Z The widespread IS200/IS605 transposon family encodes diverse programmable RNA-guided endonucleases 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 Koonin, Eugene V Zhang, Feng 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 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. 2022-04-25T17:24:22Z 2022-04-25T17:24:22Z 2021-10 2022-04-25T17:17:41Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/142061 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). en 10.1126/science.abj6856 Science Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Association for the Advancement of Science (AAAS) PMC |
| spellingShingle | 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 Koonin, Eugene V Zhang, Feng The widespread IS200/IS605 transposon family encodes diverse programmable RNA-guided endonucleases |
| title | The widespread IS200/IS605 transposon family encodes diverse programmable RNA-guided endonucleases |
| title_full | The widespread IS200/IS605 transposon family encodes diverse programmable RNA-guided endonucleases |
| title_fullStr | The widespread IS200/IS605 transposon family encodes diverse programmable RNA-guided endonucleases |
| title_full_unstemmed | The widespread IS200/IS605 transposon family encodes diverse programmable RNA-guided endonucleases |
| title_short | The widespread IS200/IS605 transposon family encodes diverse programmable RNA-guided endonucleases |
| title_sort | widespread is200 is605 transposon family encodes diverse programmable rna guided endonucleases |
| url | https://hdl.handle.net/1721.1/142061 |
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