Synthesis of wybutosine at G37 of tRNA(Phe) (Homo sapiens)

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3, 5, 7, 941, 82, 46cytoplasmnucleoplasmAdoMettRNA(Phe) containing1-methylG-37TYW5 CO2CO2SUCCAAdoHcyAdoMettRNA(Phe) containingyW-187 at 37TYW5:Fe2+ dimerTYW1 TRMT5tRNA(Phe) containingOHyW-72 at 37AdoHcyAdoMetH2OtRNA(Phe) containingyW-58 at 37AdoHcytRNA(Phe) containingOHyW at 37AdoHcyTYW1:FMN:4Fe-4SFMN tRNA(Phe) containingyW at 37tRNA(Phe) containing1-methylG-37CO2AdoMetAdoMetAdoMetL-Met2OGTYW35'-deoxyadenosineFe2+ tRNA(Phe) containingyW-86 at 37tRNA(Phe) containingG-374Fe-4S cluster AdoMettRNA(Phe) containingyW-72 at 37PYRAdoHcyO2TRMT12MTADLCMT2


Derivatives of wyosine are tricyclic bases found at nucleotide 37 of tRNA(Phe) in eukaryotes. The pathway of wybutosine synthesis begins with a templated guanosine residue and proceeds through 6 steps catalyzed by 5 enzymes: N1 methylation of guanosine, condensation of 1-methylguanosine with pyruvate to yield 4-demethylwyosine, addition of an aminocarboxypropyl group to yield yW-86, methylation of yW-86 to yield yW-72, methylation of yW-72 to yield yW-58, and methoxycarbonylation of yW-58 to yield wybutosine (reviewed in Young and Bandarian 2013, Perche-Letuvée et al. 2014). Wybutosine may further be modified by hydroxylation and methylation. Wyosine derivatives at position 37 of tRNAs participate in translational fidelity by stabilizing codon-anticodon pairing (Konevega et al. 2004) and preventing frameshifting (Waas et al. 2007). View original pathway at:Reactome.


Pathway is converted from Reactome ID: 6782861
Reactome version: 66
Reactome Author 
Reactome Author: May, Bruce

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Ontology Terms



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  1. Christian T, Gamper H, Hou YM.; ''Conservation of structure and mechanism by Trm5 enzymes.''; PubMed
  2. Kato M, Araiso Y, Noma A, Nagao A, Suzuki T, Ishitani R, Nureki O.; ''Crystal structure of a novel JmjC-domain-containing protein, TYW5, involved in tRNA modification.''; PubMed
  3. Waas WF, Druzina Z, Hanan M, Schimmel P.; ''Role of a tRNA base modification and its precursors in frameshifting in eukaryotes.''; PubMed
  4. Noma A, Ishitani R, Kato M, Nagao A, Nureki O, Suzuki T.; ''Expanding role of the jumonji C domain as an RNA hydroxylase.''; PubMed
  5. Konevega AL, Soboleva NG, Makhno VI, Semenkov YP, Wintermeyer W, Rodnina MV, Katunin VI.; ''Purine bases at position 37 of tRNA stabilize codon-anticodon interaction in the ribosomal A site by stacking and Mg2+-dependent interactions.''; PubMed
  6. Rodriguez V, Vasudevan S, Noma A, Carlson BA, Green JE, Suzuki T, Chandrasekharappa SC.; ''Structure-function analysis of human TYW2 enzyme required for the biosynthesis of a highly modified Wybutosine (yW) base in phenylalanine-tRNA.''; PubMed
  7. Perche-Letuvée P, Molle T, Forouhar F, Mulliez E, Atta M.; ''Wybutosine biosynthesis: structural and mechanistic overview.''; PubMed
  8. Brulé H, Elliott M, Redlak M, Zehner ZE, Holmes WM.; ''Isolation and characterization of the human tRNA-(N1G37) methyltransferase (TRM5) and comparison to the Escherichia coli TrmD protein.''; PubMed
  9. Young AP, Bandarian V.; ''Radical mediated ring formation in the biosynthesis of the hypermodified tRNA base wybutosine.''; PubMed


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101208view11:10, 1 November 2018ReactomeTeamreactome version 66
100746view20:35, 31 October 2018ReactomeTeamreactome version 65
100290view19:12, 31 October 2018ReactomeTeamreactome version 64
99836view15:56, 31 October 2018ReactomeTeamreactome version 63
99393view14:33, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93747view13:33, 16 August 2017ReactomeTeamreactome version 61
93266view11:18, 9 August 2017ReactomeTeamreactome version 61
88411view11:51, 5 August 2016FehrhartOntology Term : 'tRNA maturation pathway' added !
86343view09:15, 11 July 2016ReactomeTeamreactome version 56
83443view12:25, 18 November 2015ReactomeTeamNew pathway

External references


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NameTypeDatabase referenceComment
2OGMetaboliteCHEBI:16810 (ChEBI)
4Fe-4S cluster MetaboliteCHEBI:49883 (ChEBI)
5'-deoxyadenosineMetaboliteCHEBI:17319 (ChEBI)
AdoHcyMetaboliteCHEBI:16680 (ChEBI)
AdoMetMetaboliteCHEBI:15414 (ChEBI)
CO2MetaboliteCHEBI:16526 (ChEBI)
FMN MetaboliteCHEBI:17621 (ChEBI)
Fe2+ MetaboliteCHEBI:18248 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
L-MetMetaboliteCHEBI:57844 (ChEBI)
LCMT2ProteinO60294 (Uniprot-TrEMBL)
MTADMetaboliteCHEBI:17509 (ChEBI)
O2MetaboliteCHEBI:15379 (ChEBI)
PYRMetaboliteCHEBI:32816 (ChEBI)
SUCCAMetaboliteCHEBI:15741 (ChEBI)
TRMT12ProteinQ53H54 (Uniprot-TrEMBL)
TRMT5ProteinQ32P41 (Uniprot-TrEMBL)
TYW1 ProteinQ9NV66 (Uniprot-TrEMBL)
TYW1:FMN:4Fe-4SComplexR-HSA-6782882 (Reactome)
TYW3ProteinQ6IPR3 (Uniprot-TrEMBL)
TYW5 ProteinA2RUC4 (Uniprot-TrEMBL)
TYW5:Fe2+ dimerComplexR-HSA-6783460 (Reactome)
tRNA(Phe) containing 1-methylG-37R-HSA-6782902 (Reactome)
tRNA(Phe) containing 1-methylG-37R-HSA-6783390 (Reactome)
tRNA(Phe) containing G-37R-HSA-6782877 (Reactome)
tRNA(Phe) containing OHyW at 37R-HSA-6783457 (Reactome)
tRNA(Phe) containing OHyW-72 at 37R-HSA-6783496 (Reactome)
tRNA(Phe) containing yW at 37R-HSA-6782903 (Reactome)
tRNA(Phe) containing yW-187 at 37R-HSA-6782898 (Reactome)
tRNA(Phe) containing yW-58 at 37R-HSA-6782864 (Reactome)
tRNA(Phe) containing yW-72 at 37R-HSA-6782871 (Reactome)
tRNA(Phe) containing yW-86 at 37R-HSA-6782880 (Reactome)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
2OGR-HSA-6783455 (Reactome)
5'-deoxyadenosineArrowR-HSA-6782895 (Reactome)
AdoHcyArrowR-HSA-6782859 (Reactome)
AdoHcyArrowR-HSA-6782879 (Reactome)
AdoHcyArrowR-HSA-6782881 (Reactome)
AdoHcyArrowR-HSA-6782890 (Reactome)
AdoHcyArrowR-HSA-6783473 (Reactome)
AdoMetR-HSA-6782859 (Reactome)
AdoMetR-HSA-6782879 (Reactome)
AdoMetR-HSA-6782881 (Reactome)
AdoMetR-HSA-6782890 (Reactome)
AdoMetR-HSA-6782893 (Reactome)
AdoMetR-HSA-6782895 (Reactome)
AdoMetR-HSA-6783473 (Reactome)
CO2ArrowR-HSA-6782895 (Reactome)
CO2ArrowR-HSA-6783455 (Reactome)
CO2R-HSA-6782890 (Reactome)
CO2R-HSA-6783473 (Reactome)
H2OArrowR-HSA-6782895 (Reactome)
L-MetArrowR-HSA-6782895 (Reactome)
LCMT2mim-catalysisR-HSA-6782881 (Reactome)
LCMT2mim-catalysisR-HSA-6782890 (Reactome)
LCMT2mim-catalysisR-HSA-6783473 (Reactome)
MTADArrowR-HSA-6782893 (Reactome)
O2R-HSA-6783455 (Reactome)
PYRR-HSA-6782895 (Reactome)
R-HSA-6782859 (Reactome) TRMT5 transfers a methyl group from S-adenosylmethionine to the 1 position of guanosine-37 of tRNA(Phe) (Brulé et al. 2004, Christian et al. 2013). The yeast homolog, TRM5, catalyzes the same reaction.
R-HSA-6782879 (Reactome) As inferred from homologs in Saccharomyces cerevisiae, TYW3 transfers a methyl group from S-adenosylmethionine to yW-86 (7-((3S)-(3-amino-3-carboxypropyl))-4-demethylwyosine) at nucleotide 37 of tRNA(Phe), yielding yW-72 (7-((3S)-(3-amino-3-carboxypropyl))wyosine) and S-adenosylhomocysteine.
R-HSA-6782881 (Reactome) As inferred from homologues in Saccharomyces cerevisiae, LCMT2 (TYW4) transfers a methyl group from S-adenosylmethionine to yW-72 (7-((3S)-3-amino-3-carboxypropyl)wyosine) at nucleotide 37 of tRNA(Phe), yielding yW-58 (7-((3S)-3-amino-3-(methoxycarbonyl)propyl)wyosine) and S-adenosylhomocysteine.
R-HSA-6782890 (Reactome) As inferred from homologues in Saccharomyces cerevisiae, LCMT2 (TYW4) methoxycarbonylates yW-58 (7-((3S)-3-amino-3-(methoxycarbonyl)propyl)wyosine) at nucleotide 37 of tRNA(Phe) yielding yW (wybutosine). A molecule of carbon dioxide is incorporated during the reaction.
R-HSA-6782893 (Reactome) As inferred from homologs in Saccharomyces cerevisiae, TRM12 transfers an aminocarboxypropyl group from S-adenosymethionine to yW-187 (4-demethylwyosine) at nucleotide 37 of tRNA(Phe), yielding yW-86 (7-((3S)-3-amino-3-carboxypropyl)-4-demethylwyosine) and S-methyl-5'-thioadenosine.
R-HSA-6782895 (Reactome) As inferred from homologs in Saccharomyces cerevisiae, TYW1 in a complex with FMN and an iron-sulfur cluster transfers 2 carbon atoms from pyruvate to 1-methylguanosine-37 of tRNA(Phe), yielding yW-187 (4-demethylwyosine) at nucleotide 37.
R-HSA-6783455 (Reactome) TYW5 uses 2-oxoglutarate and molecular oxygen to hydroxylate yW-72 (7-(3-amino-3-carboxypropyl)wyosine) at nucleotide 37 of tRNA(Phe), yielding OHyW-72 (7-(2-hydroxy-3-amino-3-carboxypropyl)wyosine), carbon dioxide, and succinate (Noma et al. 2010, Kato et al. 2011).
R-HSA-6783473 (Reactome) LCMT2 (TYW4) methoxycarbonylates OHyW-72 (7-(2-hydroxy-3-amino-3-carboxypropyl)wyosine) at nucleotide 37 of tRNA(Phe), yielding OHyW (hydroxywybutosine) (Noma et al. 2010).
SUCCAArrowR-HSA-6783455 (Reactome)
TRMT12mim-catalysisR-HSA-6782893 (Reactome)
TRMT5mim-catalysisR-HSA-6782859 (Reactome)
TYW1:FMN:4Fe-4Smim-catalysisR-HSA-6782895 (Reactome)
TYW3mim-catalysisR-HSA-6782879 (Reactome)
TYW5:Fe2+ dimermim-catalysisR-HSA-6783455 (Reactome)
tRNA(Phe) containing 1-methylG-37ArrowR-HSA-6782859 (Reactome)
tRNA(Phe) containing 1-methylG-37R-HSA-6782895 (Reactome)
tRNA(Phe) containing G-37R-HSA-6782859 (Reactome)
tRNA(Phe) containing OHyW at 37ArrowR-HSA-6783473 (Reactome)
tRNA(Phe) containing OHyW-72 at 37ArrowR-HSA-6783455 (Reactome)
tRNA(Phe) containing OHyW-72 at 37R-HSA-6783473 (Reactome)
tRNA(Phe) containing yW at 37ArrowR-HSA-6782890 (Reactome)
tRNA(Phe) containing yW-187 at 37ArrowR-HSA-6782895 (Reactome)
tRNA(Phe) containing yW-187 at 37R-HSA-6782893 (Reactome)
tRNA(Phe) containing yW-58 at 37ArrowR-HSA-6782881 (Reactome)
tRNA(Phe) containing yW-58 at 37R-HSA-6782890 (Reactome)
tRNA(Phe) containing yW-72 at 37ArrowR-HSA-6782879 (Reactome)
tRNA(Phe) containing yW-72 at 37R-HSA-6782881 (Reactome)
tRNA(Phe) containing yW-72 at 37R-HSA-6783455 (Reactome)
tRNA(Phe) containing yW-86 at 37ArrowR-HSA-6782893 (Reactome)
tRNA(Phe) containing yW-86 at 37R-HSA-6782879 (Reactome)
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