IUBMB Enzyme Nomenclature


Accepted name: methylenetetrahydrofolate—tRNA-(uracil54-C5)-methyltransferase [NAD(P)H-oxidizing]

Reaction: 5,10-methylenetetrahydrofolate + uracil54 in tRNA + NAD(P)H + H+ = tetrahydrofolate + 5-methyluracil54 in tRNA + NAD(P)+

Glossary: Ψ = pseudouridine
T = ribothymidine = 5-methyluridine

Other name(s): folate-dependent ribothymidyl synthase; methylenetetrahydrofolate-transfer ribonucleate uracil 5-methyltransferase; 5,10-methylenetetrahydrofolate:tRNA-UΨC (uracil-5-)-methyl-transferase; 5,10-methylenetetrahydrofolate:tRNA (uracil-5-)-methyl-transferase; TrmFO; folate/FAD-dependent tRNA T54 methyltransferase; methylenetetrahydrofolate—tRNA-(uracil54-C5)-methyltransferase (FADH2-oxidizing)

Systematic name: 5,10-methylenetetrahydrofolate:tRNA (uracil54-C5)-methyltransferase

Comments: A flavoprotein (FAD). Up to 25% of the bases in mature tRNA are post-translationally modified or hypermodified. One almost universal post-translational modification is the conversion of U54 into ribothymidine in the TΨC loop, and this modification is found in most species studied to date [2]. Unlike this enzyme, which uses 5,10-methylenetetrahydrofolate and NAD(P)H to supply the atoms for methylation of U54, EC, tRNA (uracil54-C5)-methyltransferase, uses S-adenosyl-L-methionine.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 56831-74-4


1. Delk, A.S., Nagle, D.P., Jr. and Rabinowitz, J.C. Methylenetetrahydrofolate-dependent biosynthesis of ribothymidine in transfer RNA of Streptococcus faecalis. Evidence for reduction of the 1-carbon unit by FADH2. J. Biol. Chem. 255 (1980) 4387-4390. [PMID: 6768721]

2. Becker, H.F., Motorin, Y., Sissler, M., Florentz, C. and Grosjean, H. Major identity determinants for enzymatic formation of ribothymidine and pseudouridine in the TΨ-loop of yeast tRNAs. J. Mol. Biol. 274 (1997) 505-518. [PMID: 9417931]

3. Nishimasu, H., Ishitani, R., Yamashita, K., Iwashita, C., Hirata, A., Hori, H. and Nureki, O. Atomic structure of a folate/FAD-dependent tRNA T54 methyltransferase. Proc. Natl. Acad. Sci. USA 106 (2009) 8180-8185. [PMID: 19416846]

4. Yamagami, R., Yamashita, K., Nishimasu, H., Tomikawa, C., Ochi, A., Iwashita, C., Hirata, A., Ishitani, R., Nureki, O. and Hori, H. The tRNA recognition mechanism of folate/FAD-dependent tRNA methyltransferase (TrmFO). J. Biol. Chem 287 (2012) 42480-42494. [PMID: 23095745]

[EC created 1983 as EC, transferred 1984 to EC, modified 2011, modified 2019]

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