Programmable RNA-guided endonucleases are widespread in eukaryotes and their viruses.
| العنوان: | Programmable RNA-guided endonucleases are widespread in eukaryotes and their viruses. |
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| المؤلفون: | Jiang K; McGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Lim J; McGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Sgrizzi S; McGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Trinh M; McGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Kayabolen A; McGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Yutin N; National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA., Koonin EV; National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA., Abudayyeh OO; McGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Gootenberg JS; McGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. |
| المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2023 Jun 14. Date of Electronic Publication: 2023 Jun 14. |
| نوع المنشور: | Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: | TnpB proteins are RNA-guided nucleases that are broadly associated with IS200/605 family transposons in prokaryotes. TnpB homologs, named Fanzors, have been detected in genomes of some eukaryotes and large viruses, but their activity and functions in eukaryotes remain unknown. We searched genomes of diverse eukaryotes and their viruses for TnpB homologs and identified numerous putative RNA-guided nucleases that are often associated with various transposases, suggesting they are encoded in mobile genetic elements. Reconstruction of the evolution of these nucleases, which we rename Horizontally-transferred Eukaryotic RNA-guided Mobile Element Systems (HERMES), revealed multiple acquisitions of TnpBs by eukaryotes and subsequent diversification. In their adaptation and spread in eukaryotes, HERMES proteins acquired nuclear localization signals, and genes captured introns, indicating extensive, long term adaptation to functioning in eukaryotic cells. Biochemical and cellular evidence show that HERMES employ non-coding RNAs encoded adjacent to the nuclease for RNA-guided cleavage of double-stranded DNA. HERMES nucleases contain a re-arranged catalytic site of the RuvC domain, similar to a distinct subset of TnpBs, and lack collateral cleavage activity. We demonstrate that HERMES can be harnessed for genome editing in human cells, highlighting the potential of these widespread eukaryotic RNA-guided nucleases for biotechnology applications. |
| التعليقات: | Update in: Sci Adv. 2023 Sep 29;9(39):eadk0171. (PMID: 37756409) |
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| معلومات مُعتمدة: | R01 AG074932 United States AG NIA NIH HHS; R01 EB031957 United States EB NIBIB NIH HHS; R21 AI149694 United States AI NIAID NIH HHS; R56 HG011857 United States HG NHGRI NIH HHS |
| تواريخ الأحداث: | Date Created: 20230703 Latest Revision: 20231106 |
| رمز التحديث: | 20231106 |
| مُعرف محوري في PubMed: | PMC10312701 |
| DOI: | 10.1101/2023.06.13.544871 |
| PMID: | 37398409 |
| قاعدة البيانات: | MEDLINE |
| DOI: | 10.1101/2023.06.13.544871 |
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