ALKBH8-mediated formation of a novel diastereomeric pair of wobble nucleosides in mammalian tRNA
| Autor: | Lene Songe-Møller, Cathrine Broberg Vågbø, Finn Kirpekar, Pål Ø. Falnes, Hans E. Krokan, Guro Flor Lien, Erwin van den Born, Vibeke Leihne, Grazyna Leszczynska, Andrzej Malkiewicz, Arne Klungland |
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| Rok vydání: | 2011 |
| Předmět: |
DNA repair
AlkB General Physics and Astronomy Wobble base pair General Biochemistry Genetics and Molecular Biology Nucleic acid secondary structure Mice Species Specificity Tandem Mass Spectrometry Animals RNA Messenger Codon Uridine tRNA Methyltransferases Multidisciplinary biology Molecular Structure RNA Computational Biology General Chemistry RNA Transfer Gly TRNA Methyltransferases Biochemistry Protein Biosynthesis Transfer RNA Nucleic acid biology.protein AlkB Homolog 8 tRNA Methyltransferase Cattle Chromatography Liquid |
| Zdroj: | van den Born, E, Vagbo, C B, Songe-Moller, L, Leihne, V, Lien, G F, Leszczynska, G, Malkiewicz, A, Krokan, H E, Kirpekar, F, Klungland, A & Falnes, P O 2011, ' ALKBH8-mediated formation of a novel diastereomeric pair of wobble nucleosides in mammalian tRNA ', Nature Communications, vol. 2 . https://doi.org/10.1038/ncomms1173 Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/ncomms1173 |
| Popis: | Mammals have nine different homologues (ALKBH1-9) of the Escherichia coli DNA repair demethylase AlkB. ALKBH2 is a genuine DNA repair enzyme, but the in vivo function of the other ALKBH proteins has remained elusive. It was recently shown that ALKBH8 contains an additional transfer RNA ( tRNA) methyltransferase domain, which generates the wobble nucleoside 5-methoxycarbonylmethyluridine (mcm(5)U) from its precursor 5-carboxymethyluridine (cm(5)U). In this study, we report that (R)- and (S)-5-methoxycarbonylhydroxymethyluridine (mchm(5)U), hydroxylated forms of mcm(5)U, are present in mammalian tRNA(UCG)(Arg), and tRNA(UCC)(Gly), respectively, representing the first example of a diastereomeric pair of modified RNA nucleosides. Through in vitro and in vivo studies, we show that both diastereomers of mchm(5)U are generated from mcm(5)U, and that the AlkB domain of ALKBH8 specifically hydroxylates mcm(5)U into ( S)- mchm(5)U in tRNAUCCGly. These findings expand the function of the ALKBH oxygenases beyond nucleic acid repair and increase the current knowledge on mammalian wobble uridine modifications and their biogenesis. |
| Databáze: | OpenAIRE |
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