A cytosine deaminase for programmable single-base RNA editing
Programmable RNA editing enables reversible recoding of RNA information for research and disease treatment. Previously, we developed a programmable adenosine-to-inosine (A-to-I) RNA editing approach by fusing catalytically inactivate RNA-targeting CRISPR-Cas13 (dCas13) with the adenine deaminase dom...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Association for the Advancement of Science (AAAS)
2020
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| Online Access: | https://hdl.handle.net/1721.1/126395 |
| _version_ | 1826210738582061056 |
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| author | Abudayyeh, Omar O. Gootenberg, Jonathan S Franklin, Brian Koob, Jeremy Kellner, Max J. Ladha, Alim Joung, Julia Kirchgatterer, Paul Cox, David B. T. Zhang, Feng |
| author2 | McGovern Institute for Brain Research at MIT |
| author_facet | McGovern Institute for Brain Research at MIT Abudayyeh, Omar O. Gootenberg, Jonathan S Franklin, Brian Koob, Jeremy Kellner, Max J. Ladha, Alim Joung, Julia Kirchgatterer, Paul Cox, David B. T. Zhang, Feng |
| author_sort | Abudayyeh, Omar O. |
| collection | MIT |
| description | Programmable RNA editing enables reversible recoding of RNA information for research and disease treatment. Previously, we developed a programmable adenosine-to-inosine (A-to-I) RNA editing approach by fusing catalytically inactivate RNA-targeting CRISPR-Cas13 (dCas13) with the adenine deaminase domain of ADAR2. Here, we report a cytidine-to-uridine (C-to-U) RNA editor, referred to as RNA Editing for Specific C-to-U Exchange (RESCUE), by directly evolving ADAR2 into a cytidine deaminase. RESCUE doubles the number of mutations targetable by RNA editing and enables modulation of phosphosignaling-relevant residues. We apply RESCUE to drive b-catenin activation and cellular growth. Furthermore, RESCUE retains A-to-I editing activity, enabling multiplexed C-to-U and A-to-I editing through the use of tailored guide RNAs. |
| first_indexed | 2024-09-23T14:54:55Z |
| format | Article |
| id | mit-1721.1/126395 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:54:55Z |
| publishDate | 2020 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/1263952022-10-01T23:18:32Z A cytosine deaminase for programmable single-base RNA editing Abudayyeh, Omar O. Gootenberg, Jonathan S Franklin, Brian Koob, Jeremy Kellner, Max J. Ladha, Alim Joung, Julia Kirchgatterer, Paul Cox, David B. T. Zhang, Feng McGovern Institute for Brain Research at MIT Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Programmable RNA editing enables reversible recoding of RNA information for research and disease treatment. Previously, we developed a programmable adenosine-to-inosine (A-to-I) RNA editing approach by fusing catalytically inactivate RNA-targeting CRISPR-Cas13 (dCas13) with the adenine deaminase domain of ADAR2. Here, we report a cytidine-to-uridine (C-to-U) RNA editor, referred to as RNA Editing for Specific C-to-U Exchange (RESCUE), by directly evolving ADAR2 into a cytidine deaminase. RESCUE doubles the number of mutations targetable by RNA editing and enables modulation of phosphosignaling-relevant residues. We apply RESCUE to drive b-catenin activation and cellular growth. Furthermore, RESCUE retains A-to-I editing activity, enabling multiplexed C-to-U and A-to-I editing through the use of tailored guide RNAs. National Institutes of Health (Grants 1F30-CA210382, 1R01-HG009761, 1R01-MH110049, and 1DP1-HL141201) 2020-07-27T13:39:01Z 2020-07-27T13:39:01Z 2019-07 2019-04 2019-10-08T13:30:14Z Article http://purl.org/eprint/type/JournalArticle 0036-8075 1095-9203 https://hdl.handle.net/1721.1/126395 Abudayyeh, Omar O. et al. "A cytosine deaminase for programmable single-base RNA editing." Science 365, 6451 (July 2019): 382-386 © 2019 American Association for the Advancement of Science en http://dx.doi.org/10.1126/science.aax7063 Science Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Association for the Advancement of Science (AAAS) Other repository |
| spellingShingle | Abudayyeh, Omar O. Gootenberg, Jonathan S Franklin, Brian Koob, Jeremy Kellner, Max J. Ladha, Alim Joung, Julia Kirchgatterer, Paul Cox, David B. T. Zhang, Feng A cytosine deaminase for programmable single-base RNA editing |
| title | A cytosine deaminase for programmable single-base RNA editing |
| title_full | A cytosine deaminase for programmable single-base RNA editing |
| title_fullStr | A cytosine deaminase for programmable single-base RNA editing |
| title_full_unstemmed | A cytosine deaminase for programmable single-base RNA editing |
| title_short | A cytosine deaminase for programmable single-base RNA editing |
| title_sort | cytosine deaminase for programmable single base rna editing |
| url | https://hdl.handle.net/1721.1/126395 |
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