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Updated: May 16, 2026

Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues
Published on: November 22, 2014
FAD/folate-dependent tRNA methyltransferase: flavin as a new methyl-transfer agent
Djemel Hamdane1, Manuela Argentini, David Cornu
1Laboratoire de Chimie des Processus Biologiques, CNRS-FRE 3488, Collège De France, 11 place Marcelin Berthelot, 75231 Paris Cedex 05, France. djemel.hamdane@college-de-france.fr
Abstract:
RNAs contain structurally and functionally important modified nucleosides. Methylation, the most frequent RNA modification in all living organisms, mostly relies on SAM (S-adenosylmethionine)-dependent methyltransferases. TrmFO was recently discovered as a unique tRNA methyltransferase using instead methylenetetrahydrofolate and reduced flavin adenine dinucleotide (FAD) as essential cofactors, but its mechanism has remained elusive. Here, we report that TrmFO carries an active tRNA-methylating agent and characterize it as an original enzyme-methylene-FAD covalent adduct by mass spectrometry and a combination of spectroscopic and biochemical methods. Our data support a novel tRNA methylating mechanism.
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