MetaCyc Pathway: tRNA methylation (yeast)
Traceable author statement to experimental support

Pathway diagram: tRNA methylation (yeast)

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: BiosynthesisNucleosides and Nucleotides BiosynthesisNucleic Acid Processing
Metabolic Clusters

Some taxa known to possess this pathway include : Saccharomyces cerevisiae

Expected Taxonomic Range: Eukaryota

RNA modification is a post-transcriptional process by which certain nucleotides are altered after their initial incorporation into an RNA chain. The most heavily modified class of RNA molecules is the tRNA - an average of 11%, 14%, and 17% of the tRNA residues are modified in Escherichia coli, Saccharomyces cerevisiae, and mammalian cytoplasm, respectively [Sprinzl98]. These modifications expand the chemical and functional diversity of tRNA, and enhance its structural stability [Bjork87]. In some bacterial genomes, about 1% of the coding genes are devoted to tRNA modification [Bjork87].

One of the most common modifications of tRNA bases is methylation. Methylation is known to help control tRNA folding, to ensure decoding specificity during translation of the genetic code, and to enhance aminoacylation by certain tRNA synthetases. In the great majority of cases, the methyl group is derived from S-adenosyl-L-methionine (SAM), linking tRNA modifications to the intermediary metabolism of this cofactor.

SAM-dependent methyltransferases have been divided into five structural classes (I-V) based on their active-site folds [Schubert03]. The vast majority of the known enzymes that catalyze tRNA nucleotide base methylation belong to class I, with the remainder belonging to class IV.

Class I enzymes feature the ancient Rossmann-fold, consisting largely of a parallel β-sheet with α-helical crossovers. A final β strand is oriented in an anti-parallel direction relative to the others. Class IV enzymes, also known as the SPOUT family of RNA methyltransferases [Anantharaman02], have a structural core made up of six parallel β-strands, with the final three folded into a rare protein subdomain known as a deep trefoil knot. Another characteristic feature of the class IV structure is that the active site is assembled at the interface of a homodimer, in which both monomers contribute to the cofactor binding [Ahn03, Elkins03].

Methylation of a specific tRNA nucleotide base is sequence-dependent and varies greatly from species to species for different amino acid acceptors, and even among the three domains of life for the same amino acid acceptor [Hou10].

Created 29-Jun-2011 by Caspi R, SRI International


Ahn03: Ahn HJ, Kim HW, Yoon HJ, Lee BI, Suh SW, Yang JK (2003). "Crystal structure of tRNA(m1G37)methyltransferase: insights into tRNA recognition." EMBO J 22(11);2593-603. PMID: 12773376

Anantharaman02: Anantharaman V, Koonin EV, Aravind L (2002). "SPOUT: a class of methyltransferases that includes spoU and trmD RNA methylase superfamilies, and novel superfamilies of predicted prokaryotic RNA methylases." J Mol Microbiol Biotechnol 4(1);71-5. PMID: 11763972

Bjork87: Bjork GR, Ericson JU, Gustafsson CE, Hagervall TG, Jonsson YH, Wikstrom PM (1987). "Transfer RNA modification." Annu Rev Biochem 56;263-87. PMID: 3304135

Elkins03: Elkins PA, Watts JM, Zalacain M, van Thiel A, Vitazka PR, Redlak M, Andraos-Selim C, Rastinejad F, Holmes WM (2003). "Insights into catalysis by a knotted TrmD tRNA methyltransferase." J Mol Biol 333(5);931-49. PMID: 14583191

Hou10: Hou YM, Perona JJ (2010). "Stereochemical mechanisms of tRNA methyltransferases." FEBS Lett 584(2);278-86. PMID: 19944101

Schubert03: Schubert HL, Blumenthal RM, Cheng X (2003). "Many paths to methyltransfer: a chronicle of convergence." Trends Biochem Sci 28(6);329-35. PMID: 12826405

Sprinzl98: Sprinzl M, Horn C, Brown M, Ioudovitch A, Steinberg S (1998). "Compilation of tRNA sequences and sequences of tRNA genes." Nucleic Acids Res 26(1);148-53. PMID: 9399820

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Anderson00: Anderson J, Phan L, Hinnebusch AG (2000). "The Gcd10p/Gcd14p complex is the essential two-subunit tRNA(1-methyladenosine) methyltransferase of Saccharomyces cerevisiae." Proc Natl Acad Sci U S A 97(10);5173-8. PMID: 10779558

Anderson98: Anderson J, Phan L, Cuesta R, Carlson BA, Pak M, Asano K, Bjork GR, Tamame M, Hinnebusch AG (1998). "The essential Gcd10p-Gcd14p nuclear complex is required for 1-methyladenosine modification and maturation of initiator methionyl-tRNA." Genes Dev 12(23);3650-62. PMID: 9851972

Bjork01: Bjork GR, Jacobsson K, Nilsson K, Johansson MJ, Bystrom AS, Persson OP (2001). "A primordial tRNA modification required for the evolution of life?." EMBO J 20(1-2);231-9. PMID: 11226173

Brule04: Brule H, Elliott M, Redlak M, Zehner ZE, Holmes WM (2004). "Isolation and characterization of the human tRNA-(N1G37) methyltransferase (TRM5) and comparison to the Escherichia coli TrmD protein." Biochemistry 43(28);9243-55. PMID: 15248782

Brzezicha06: Brzezicha B, Schmidt M, Makalowska I, Jarmolowski A, Pienkowska J, Szweykowska-Kulinska Z (2006). "Identification of human tRNA:m5C methyltransferase catalysing intron-dependent m5C formation in the first position of the anticodon of the pre-tRNA Leu (CAA)." Nucleic Acids Res 34(20);6034-43. PMID: 17071714

Cuesta98: Cuesta R, Hinnebusch AG, Tamame M (1998). "Identification of GCD14 and GCD15, novel genes required for translational repression of GCN4 mRNA in Saccharomyces cerevisiae." Genetics 148(3);1007-20. PMID: 9539420

deCrecyLagard10: de Crecy-Lagard V, Brochier-Armanet C, Urbonavicius J, Fernandez B, Phillips G, Lyons B, Noma A, Alvarez S, Droogmans L, Armengaud J, Grosjean H (2010). "Biosynthesis of wyosine derivatives in tRNA: an ancient and highly diverse pathway in Archaea." Mol Biol Evol 27(9);2062-77. PMID: 20382657

Droogmans87: Droogmans L, Grosjean H (1987). "Enzymatic conversion of guanosine 3' adjacent to the anticodon of yeast tRNAPhe to N1-methylguanosine and the wye nucleoside: dependence on the anticodon sequence." EMBO J 6(2);477-83. PMID: 3556165

Feldmann94: Feldmann H, Aigle M, Aljinovic G, Andre B, Baclet MC, Barthe C, Baur A, Becam AM, Biteau N, Boles E (1994). "Complete DNA sequence of yeast chromosome II." EMBO J 13(24);5795-809. PMID: 7813418

GarciaBarrio95: Garcia-Barrio MT, Naranda T, Vazquez de Aldana CR, Cuesta R, Hinnebusch AG, Hershey JW, Tamame M (1995). "GCD10, a translational repressor of GCN4, is the RNA-binding subunit of eukaryotic translation initiation factor-3." Genes Dev 9(14);1781-96. PMID: 7542616

Kalhor03: Kalhor HR, Clarke S (2003). "Novel methyltransferase for modified uridine residues at the wobble position of tRNA." Mol Cell Biol 23(24);9283-92. PMID: 14645538

Kotelawala08: Kotelawala L, Grayhack EJ, Phizicky EM (2008). "Identification of yeast tRNA Um(44) 2'-O-methyltransferase (Trm44) and demonstration of a Trm44 role in sustaining levels of specific tRNA(Ser) species." RNA 14(1);158-69. PMID: 18025252

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Lee07: Lee C, Kramer G, Graham DE, Appling DR (2007). "Yeast mitochondrial initiator tRNA is methylated at guanosine 37 by the Trm5-encoded tRNA (guanine-N1-)-methyltransferase." J Biol Chem 282(38);27744-53. PMID: 17652090

Liu98: Liu J, Straby KB (1998). "Point and deletion mutations eliminate one or both methyl group transfers catalysed by the yeast TRM1 encoded tRNA (m22G26)dimethyltransferase." Nucleic Acids Res 26(22);5102-8. PMID: 9801306

Motorin99: Motorin Y, Grosjean H (1999). "Multisite-specific tRNA:m5C-methyltransferase (Trm4) in yeast Saccharomyces cerevisiae: identification of the gene and substrate specificity of the enzyme." RNA 5(8);1105-18. PMID: 10445884

Pintard02: Pintard L, Lecointe F, Bujnicki JM, Bonnerot C, Grosjean H, Lapeyre B (2002). "Trm7p catalyses the formation of two 2'-O-methylriboses in yeast tRNA anticodon loop." EMBO J 21(7);1811-20. PMID: 11927565

Purushothaman05: Purushothaman SK, Bujnicki JM, Grosjean H, Lapeyre B (2005). "Trm11p and Trm112p are both required for the formation of 2-methylguanosine at position 10 in yeast tRNA." Mol Cell Biol 25(11);4359-70. PMID: 15899842

Van94: Van Dyck L, Jonniaux JL, de Melo Barreiros T, Kleine K, Goffeau A (1994). "Analysis of a 17.4 kb DNA segment of yeast chromosome II encompassing the ribosomal protein L19 as well as proteins with homologies to components of the hnRNP and snRNP complexes and to the human proliferation-associated p120 antigen." Yeast 10(12);1663-73. PMID: 7725803

Wilkinson07: Wilkinson ML, Crary SM, Jackman JE, Grayhack EJ, Phizicky EM (2007). "The 2'-O-methyltransferase responsible for modification of yeast tRNA at position 4." RNA 13(3);404-13. PMID: 17242307

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by Pathway Tools version 19.5 (software by SRI International) on Wed May 4, 2016, biocyc13.