Sequential action of a tRNA base editor in conversion of cytidine to pseudouridine
<jats:title>Abstract</jats:title><jats:p>Post-transcriptional RNA editing modulates gene expression in a condition-dependent fashion. We recently discovered C-to-Ψ editing in <jats:italic>Vibrio cholerae</jats:italic> tRNA. Here, we characterize the biogenesis, regulati...
| Main Authors: | , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Springer Science and Business Media LLC
2023
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| Online Access: | https://hdl.handle.net/1721.1/147794 |
| _version_ | 1826217447330414592 |
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| author | Kimura, Satoshi Srisuknimit, Veerasak McCarty, Kacie L Dedon, Peter C Kranzusch, Philip J Waldor, Matthew K |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Kimura, Satoshi Srisuknimit, Veerasak McCarty, Kacie L Dedon, Peter C Kranzusch, Philip J Waldor, Matthew K |
| author_sort | Kimura, Satoshi |
| collection | MIT |
| description | <jats:title>Abstract</jats:title><jats:p>Post-transcriptional RNA editing modulates gene expression in a condition-dependent fashion. We recently discovered C-to-Ψ editing in <jats:italic>Vibrio cholerae</jats:italic> tRNA. Here, we characterize the biogenesis, regulation, and functions of this previously undescribed RNA editing process. We show that an enzyme, TrcP, mediates the editing of C-to-U followed by the conversion of U to Ψ, consecutively. AlphaFold-2 predicts that TrcP consists of two globular domains (cytidine deaminase and pseudouridylase) and a long helical domain. The latter domain tethers tRNA substrates during both the C-to-U editing and pseudouridylation, likely enabling a substrate channeling mechanism for efficient catalysis all the way to the terminal product. C-to-Ψ editing both requires and suppresses other modifications, creating an interdependent network of modifications in the tRNA anticodon loop that facilitates coupling of tRNA modification states to iron availability. Our findings provide mechanistic insights into an RNA editing process that likely promotes environmental adaptation.</jats:p> |
| first_indexed | 2024-09-23T17:03:48Z |
| format | Article |
| id | mit-1721.1/147794 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T17:03:48Z |
| publishDate | 2023 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1477942023-02-01T03:01:26Z Sequential action of a tRNA base editor in conversion of cytidine to pseudouridine Kimura, Satoshi Srisuknimit, Veerasak McCarty, Kacie L Dedon, Peter C Kranzusch, Philip J Waldor, Matthew K Massachusetts Institute of Technology. Department of Biological Engineering <jats:title>Abstract</jats:title><jats:p>Post-transcriptional RNA editing modulates gene expression in a condition-dependent fashion. We recently discovered C-to-Ψ editing in <jats:italic>Vibrio cholerae</jats:italic> tRNA. Here, we characterize the biogenesis, regulation, and functions of this previously undescribed RNA editing process. We show that an enzyme, TrcP, mediates the editing of C-to-U followed by the conversion of U to Ψ, consecutively. AlphaFold-2 predicts that TrcP consists of two globular domains (cytidine deaminase and pseudouridylase) and a long helical domain. The latter domain tethers tRNA substrates during both the C-to-U editing and pseudouridylation, likely enabling a substrate channeling mechanism for efficient catalysis all the way to the terminal product. C-to-Ψ editing both requires and suppresses other modifications, creating an interdependent network of modifications in the tRNA anticodon loop that facilitates coupling of tRNA modification states to iron availability. Our findings provide mechanistic insights into an RNA editing process that likely promotes environmental adaptation.</jats:p> 2023-01-31T13:52:47Z 2023-01-31T13:52:47Z 2022 2023-01-31T13:47:48Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/147794 Kimura, Satoshi, Srisuknimit, Veerasak, McCarty, Kacie L, Dedon, Peter C, Kranzusch, Philip J et al. 2022. "Sequential action of a tRNA base editor in conversion of cytidine to pseudouridine." Nature Communications, 13 (1). en 10.1038/S41467-022-33714-X Nature Communications Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Nature |
| spellingShingle | Kimura, Satoshi Srisuknimit, Veerasak McCarty, Kacie L Dedon, Peter C Kranzusch, Philip J Waldor, Matthew K Sequential action of a tRNA base editor in conversion of cytidine to pseudouridine |
| title | Sequential action of a tRNA base editor in conversion of cytidine to pseudouridine |
| title_full | Sequential action of a tRNA base editor in conversion of cytidine to pseudouridine |
| title_fullStr | Sequential action of a tRNA base editor in conversion of cytidine to pseudouridine |
| title_full_unstemmed | Sequential action of a tRNA base editor in conversion of cytidine to pseudouridine |
| title_short | Sequential action of a tRNA base editor in conversion of cytidine to pseudouridine |
| title_sort | sequential action of a trna base editor in conversion of cytidine to pseudouridine |
| url | https://hdl.handle.net/1721.1/147794 |
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