CoChat
Sign Up
Cited by 23RNA regulation and diseaseRNA and protein synthesis mechanismsRNA modifications and cancer

The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.

Sequential action of a tRNA base editor in conversion of cytidine to pseudouridine

Open access
Kimura, Satoshi, Srisuknimit, Veerasak, McCarty, Kacie L., Dedon, Peter C., Kranzusch, Philip J., Waldor, Matthew K.·2022·Nature Communications
DOI 10.1038/s41467-022-33714-xPMC PMC9553926

Published version of a preprint

Open this paper in CoChat — free accountOpen PDF

Abstract

Post-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.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41467-022-33714-x

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 50

  1. Bjork, G. R. & Hagervall, T. G. Transfer RNA modification: presence, synthesis, and function. EcoSal Plus 6, https://doi.org/10.1128/ecosalplus.ESP-0007-2013 (2014). · DOI
  2. Machnicka, M. A. et al. MODOMICS: a database of RNA modification pathways-−2013 update. Nucleic Acids Res. 41, D262–D267 (2013). · DOI
  3. Wiener, D. & Schwartz, S. The epitranscriptome beyond m(6)A. Nat. Rev. Genet., https://doi.org/10.1038/s41576-020-00295-8 (2020). · DOI
  4. Ichinose, M. & Sugita, M. RNA Editing and Its Molecular Mechanism in Plant Organelles. Genes (Basel) 8, https://doi.org/10.3390/genes8010005 (2016). · DOI
  5. Eisenberg, E. & Levanon, E. Y. A-to-I RNA editing - immune protector and transcriptome diversifier. Nat. Rev. Genet 19, 473–490 (2018). · DOI
  6. Liddicoat, B. J. et al. RNA editing by ADAR1 prevents MDA5 sensing of endogenous dsRNA as nonself. Science 349, 1115–1120 (2015). · DOI
  7. Wolf, J., Gerber, A. P. & Keller, W. tadA, an essential tRNA-specific adenosine deaminase from Escherichia coli. EMBO J. 21, 3841–3851 (2002). · DOI
  8. Wang, Q., Khillan, J., Gadue, P. & Nishikura, K. Requirement of the RNA editing deaminase ADAR1 gene for embryonic erythropoiesis. Science 290, 1765–1768 (2000). · DOI
  9. Juhling, F. et al. tRNAdb 2009: compilation of tRNA sequences and tRNA genes. Nucleic Acids Res. 37, D159–D162 (2009). · DOI
  10. Murphy, F. V. T. & Ramakrishnan, V. Structure of a purine-purine wobble base pair in the decoding center of the ribosome. Nat. Struct. Mol. Biol. 11, 1251–1252 (2004). · DOI
  11. Crick, F. H. Codon-anticodon pairing: the wobble hypothesis. J. Mol. Biol. 19, 548–555 (1966). · DOI · Paper page
  12. Borner, G. V., Morl, M., Janke, A. & Paabo, S. RNA editing changes the identity of a mitochondrial tRNA in marsupials. EMBO J. 15, 5949–5957 (1996). · DOI
  13. Janke, A. & Paabo, S. Editing of a tRNA anticodon in marsupial mitochondria changes its codon recognition. Nucleic Acids Res. 21, 1523–1525 (1993). · DOI
  14. Randau, L. et al. A cytidine deaminase edits C to U in transfer RNAs in Archaea. Science 324, 657–659 (2009). · DOI
  15. Dixit, S., Henderson, J. C. & Alfonzo, J. D. Multi-substrate specificity and the evolutionary basis for interdependence in tRNA editing and methylation enzymes. Front Genet. 10, 104 (2019). · DOI
  16. Bass, B. L. RNA editing by adenosine deaminases that act on RNA. Annu Rev. Biochem 71, 817–846 (2002). · DOI
  17. Gerber, A. P. & Keller, W. An adenosine deaminase that generates inosine at the wobble position of tRNAs. Science 286, 1146–1149 (1999). · DOI
  18. Gerber, A., Grosjean, H., Melcher, T. & Keller, W. Tad1p, a yeast tRNA-specific adenosine deaminase, is related to the mammalian pre-mRNA editing enzymes ADAR1 and ADAR2. EMBO J. 17, 4780–4789 (1998). · DOI
  19. Maas, S., Gerber, A. P. & Rich, A. Identification and characterization of a human tRNA-specific adenosine deaminase related to the ADAR family of pre-mRNA editing enzymes. Proc. Natl. Acad. Sci. USA 96, 8895–8900 (1999). · DOI
  20. Lerner, T., Papavasiliou, F. N. & Pecori, R. RNA Editors, Cofactors, and mRNA Targets: An Overview of the C-to-U RNA editing machinery and its implication in human disease. Genes (Basel) 10, https://doi.org/10.3390/genes10010013 (2018). · DOI
  21. Smith, A. A., Carlow, D. C., Wolfenden, R. & Short, S. A. Mutations affecting transition-state stabilization by residues coordinating zinc at the active site of cytidine deaminase. Biochemistry 33, 6468–6474 (1994). · DOI
  22. Finn, R. D. et al. InterPro in 2017-beyond protein family and domain annotations. Nucleic Acids Res. 45, D190–D199 (2017). · DOI
  23. Kimura, S., Dedon, P. C. & Waldor, M. K. Comparative tRNA sequencing and RNA mass spectrometry for surveying tRNA modifications. Nat. Chem. Biol. 16, 964–972 (2020). · DOI
  24. Suzuki, T. & Suzuki, T. A complete landscape of post-transcriptional modifications in mammalian mitochondrial tRNAs. Nucleic Acids Res. 42, 7346–7357 (2014). · DOI
  25. Hoang, C. et al. Crystal structure of pseudouridine synthase RluA: indirect sequence readout through protein-induced RNA structure. Mol. Cell 24, 535–545 (2006). · DOI
  26. Mirdita, M. et al. ColabFold: Making protein folding accessible to all. Nat. Methods 19, 679–682 (2022). · DOI · Paper page
  27. Holm, L. Using dali for protein structure comparison. Methods Mol. Biol. 2112, 29–42 (2020). · DOI
  28. Rubio, M. A. et al. Editing and methylation at a single site by functionally interdependent activities. Nature 542, 494–497 (2017). · DOI
  29. Polson, A. G., Crain, P. F., Pomerantz, S. C., McCloskey, J. A. & Bass, B. L. The mechanism of adenosine to inosine conversion by the double-stranded RNA unwinding/modifying activity: a high-performance liquid chromatography-mass spectrometry analysis. Biochemistry 30, 11507–11514 (1991). · DOI
  30. Betts, L., Xiang, S., Short, S. A., Wolfenden, R. & Carter, C. W. Jr. Cytidine deaminase. The 2.3 A crystal structure of an enzyme: transition-state analog complex. J. Mol. Biol. 235, 635–656 (1994). · DOI
  31. Wilson, D. K., Rudolph, F. B. & Quiocho, F. A. Atomic structure of adenosine deaminase complexed with a transition-state analog: understanding catalysis and immunodeficiency mutations. Science 252, 1278–1284 (1991). · DOI
  32. Han, L. & Phizicky, E. M. A rationale for tRNA modification circuits in the anticodon loop. RNA 24, 1277–1284 (2018). · DOI
  33. Barraud, P. & Tisne, C. To be or not to be modified: Miscellaneous aspects influencing nucleotide modifications in tRNAs. IUBMB Life 71, 1126–1140 (2019). · DOI
  34. Pierrel, F., Douki, T., Fontecave, M. & Atta, M. MiaB protein is a bifunctional radical-S-adenosylmethionine enzyme involved in thiolation and methylation of tRNA. J. Biol. Chem. 279, 47555–47563 (2004). · DOI
  35. Griffiths, E. & Humphreys, J. Alterations in tRNAs containing 2-methylthio-N6-(delta2-isopentenyl)-adenosine during growth of enteropathogenic Escherichia coli in the presence of iron-binding proteins. Eur. J. Biochem 82, 503–513 (1978). · DOI
  36. Urbonavicius, J., Qian, Q., Durand, J. M., Hagervall, T. G. & Bjork, G. R. Improvement of reading frame maintenance is a common function for several tRNA modifications. EMBO J. 20, 4863–4873 (2001). · DOI
  37. Sakai, Y., Kimura, S. & Suzuki, T. Dual pathways of tRNA hydroxylation ensure efficient translation by expanding decoding capability. Nat. Commun. 10, 2858 (2019). · DOI
  38. Ito, T. & Yokoyama, S. Two enzymes bound to one transfer RNA assume alternative conformations for consecutive reactions. Nature 467, 612–616 (2010). · DOI
  39. Liu, Y. et al. Ancient translation factor is essential for tRNA-dependent cysteine biosynthesis in methanogenic archaea. Proc. Natl Acad. Sci. USA 111, 10520–10525 (2014). · DOI
  40. Ishida, K. et al. Pseudouridine at position 55 in tRNA controls the contents of other modified nucleotides for low-temperature adaptation in the extreme-thermophilic eubacterium Thermus thermophilus. Nucleic Acids Res. 39, 2304–2318 (2011). · DOI
  41. Hernandez, H. L. et al. MiaB, a bifunctionalradical-S-adenosylmethionine enzyme involved in the thiolation and methylationof tRNA, contains two essential [4Fe-4S] clusters. Biochemistry 46, 5140–5147 (2007). · DOI
  42. Millet, Y. A. et al. Insights into Vibrio cholerae intestinal colonization from monitoring fluorescently labeled bacteria. PLoS Pathog. 10, e1004405 (2014). · DOI
  43. Cameron, D. E., Urbach, J. M. & Mekalanos, J. J. A defined transposon mutant library and its use in identifying motility genes in Vibrio cholerae. Proc. Natl. Acad. Sci. USA 105, 8736–8741 (2008). · DOI
  44. Kimura, S. & Waldor, M. K. The RNA degradosome promotes tRNA quality control through clearance of hypomodified tRNA. Proc. Natl. Acad. Sci. USA 116, 1394–1403 (2019). · DOI
  45. Zhou, W. et al. Structure of the human cGAS-DNA complex reveals enhanced control of immune surveillance. Cell 174, 300–311 e311 (2018). · DOI
  46. Letunic, I. & Bork, P. Interactive Tree Of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation. Nucleic Acids Res. 49, W293–W296 (2021). · DOI
  47. Larkin, M. A. et al. Clustal W and Clustal X version 2.0. Bioinformatics 23, 2947–2948 (2007). · DOI
  48. Hall, T. A. BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symp. Ser. 41, 95–98 (1999).
  49. Zhou, W., Richmond-Buccola, D., Wang, Q. & Kranzusch, P. J. Structural basis of human TREX1 DNA degradation and autoimmune disease. Nat. Commun. 13, 4277 (2022). · DOI
  50. Hemphill, W. O., Salsbury, F. R. & Perrino, F. W. Towards a new model for the TREX1 exonuclease. bioRxiv, https://doi.org/10.1101/2022.02.25.481063 (2022). · DOI

Metadata

Authors
Kimura, S., Srisuknimit, V., McCarty, K. L., Dedon, P. C., Kranzusch, P. J., & Waldor, M. K.
Affiliations
  • Brigham and Women's Hospital (US)
  • Harvard University (US)
  • Singapore-MIT Alliance for Research and Technology (SG)
Corresponding author
Waldor, Matthew K.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2022-10-11
Volume
13
Issue
1
Pages
5994-5994
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-022-33714-x
PMC
PMC9553926
OpenAlex
W4304191875
Cited by
23
References
3
Citations by year
2025: 3 · 2024: 10 · 2023: 10
FWCI
1.88
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (AI-042347)
  • Howard Hughes Medical Institute (MKW)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
Keywords
pseudouridylation, Vibrio cholerae, tRNA anticodon loop, cytidine deaminase, substrate channeling, iron availability, protein structure prediction
MeSH terms
Anticodon, Cytidine, Cytidine Deaminase, Iron, Pseudouridine, RNA, Transfer

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review