Cargando…
Programmable RNA-guided endonucleases are widespread in eukaryotes and their viruses
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...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10312701/ https://www.ncbi.nlm.nih.gov/pubmed/37398409 http://dx.doi.org/10.1101/2023.06.13.544871 |
_version_ | 1785066972497575936 |
---|---|
author | Jiang, Kaiyi Lim, Justin Sgrizzi, Samantha Trinh, Michael Kayabolen, Alisan Yutin, Natalya Koonin, Eugene V. Abudayyeh, Omar O. Gootenberg, Jonathan S. |
author_facet | Jiang, Kaiyi Lim, Justin Sgrizzi, Samantha Trinh, Michael Kayabolen, Alisan Yutin, Natalya Koonin, Eugene V. Abudayyeh, Omar O. Gootenberg, Jonathan S. |
author_sort | Jiang, Kaiyi |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10312701 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-103127012023-07-01 Programmable RNA-guided endonucleases are widespread in eukaryotes and their viruses Jiang, Kaiyi Lim, Justin Sgrizzi, Samantha Trinh, Michael Kayabolen, Alisan Yutin, Natalya Koonin, Eugene V. Abudayyeh, Omar O. Gootenberg, Jonathan S. bioRxiv Article 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. Cold Spring Harbor Laboratory 2023-06-14 /pmc/articles/PMC10312701/ /pubmed/37398409 http://dx.doi.org/10.1101/2023.06.13.544871 Text en https://creativecommons.org/licenses/by-nc/4.0/It is made available under aCC-BY-NC 4.0 International license. |
spellingShingle | Article Jiang, Kaiyi Lim, Justin Sgrizzi, Samantha Trinh, Michael Kayabolen, Alisan Yutin, Natalya Koonin, Eugene V. Abudayyeh, Omar O. Gootenberg, Jonathan S. Programmable RNA-guided endonucleases are widespread in eukaryotes and their viruses |
title | Programmable RNA-guided endonucleases are widespread in eukaryotes and their viruses |
title_full | Programmable RNA-guided endonucleases are widespread in eukaryotes and their viruses |
title_fullStr | Programmable RNA-guided endonucleases are widespread in eukaryotes and their viruses |
title_full_unstemmed | Programmable RNA-guided endonucleases are widespread in eukaryotes and their viruses |
title_short | Programmable RNA-guided endonucleases are widespread in eukaryotes and their viruses |
title_sort | programmable rna-guided endonucleases are widespread in eukaryotes and their viruses |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10312701/ https://www.ncbi.nlm.nih.gov/pubmed/37398409 http://dx.doi.org/10.1101/2023.06.13.544871 |
work_keys_str_mv | AT jiangkaiyi programmablernaguidedendonucleasesarewidespreadineukaryotesandtheirviruses AT limjustin programmablernaguidedendonucleasesarewidespreadineukaryotesandtheirviruses AT sgrizzisamantha programmablernaguidedendonucleasesarewidespreadineukaryotesandtheirviruses AT trinhmichael programmablernaguidedendonucleasesarewidespreadineukaryotesandtheirviruses AT kayabolenalisan programmablernaguidedendonucleasesarewidespreadineukaryotesandtheirviruses AT yutinnatalya programmablernaguidedendonucleasesarewidespreadineukaryotesandtheirviruses AT koonineugenev programmablernaguidedendonucleasesarewidespreadineukaryotesandtheirviruses AT abudayyehomaro programmablernaguidedendonucleasesarewidespreadineukaryotesandtheirviruses AT gootenbergjonathans programmablernaguidedendonucleasesarewidespreadineukaryotesandtheirviruses |