Sequential action of a tRNA base editor in conversion of cytidine to pseudouridine
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s41467-022-33714-x.pdf
Description
Published version
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3.24 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Kimura, Satoshi
Srisuknimit, Veerasak
McCarty, Kacie L
Dedon, Peter C
Kranzusch, Philip J
Waldor, Matthew K
Date Issued
2022
Journal
Nature Communications
Publisher
Springer Science and Business Media LLC
Citation
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).
Version
Final published version
Abstract
AbstractPost-transcriptional RNA editing modulates gene expression in a condition-dependent fashion. We recently discovered C-to-Ψ editing in Vibrio cholerae 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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1038/S41467-022-33714-X
