2. Academic Validation
  3. ALKBH8-mediated formation of a novel diastereomeric pair of wobble nucleosides in mammalian tRNA

ALKBH8-mediated formation of a novel diastereomeric pair of wobble nucleosides in mammalian tRNA

  • Nat Commun. 2011 Feb 1;2:172. doi: 10.1038/ncomms1173.
Erwin van den Born 1,  Cathrine B Vågbø,  Lene Songe-Møller,  Vibeke Leihne,  Guro F Lien,  Grazyna Leszczynska,  Andrzej Malkiewicz,  Hans E Krokan,  Finn Kirpekar,  Arne Klungland,  Pål Ø Falnes
Affiliations

Affiliation

  • 1 Department of Molecular Biosciences, University of Oslo, PO Box 1041 Blindern, Oslo 0316, Norway.
PMID: 21285950 DOI: 10.1038/ncomms1173
Abstract

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 5-methoxycarbonylhydroxymethyluridine (mchm(5)U), hydroxylated forms of mcm(5)U, are present in mammalian tRNA-Arg(UCG), and tRNA-Gly(UCC), 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 tRNA-Gly(UCC). 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.

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