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

Author

Listed:
  • Erwin van den Born

    (University of Oslo, PO Box 1041 Blindern, Oslo 0316, Norway.)

  • Cathrine B. Vågbø

    (Norwegian University of Science and Technology)

  • Lene Songe-Møller

    (Centre for Molecular Biology and Neuroscience, Institute of Medical Microbiology, Oslo University Hospital)

  • Vibeke Leihne

    (University of Oslo, PO Box 1041 Blindern, Oslo 0316, Norway.)

  • Guro F. Lien

    (Centre for Molecular Biology and Neuroscience, Institute of Medical Microbiology, Oslo University Hospital)

  • Grazyna Leszczynska

    (Institute of Organic Chemistry, Technical University)

  • Andrzej Malkiewicz

    (Institute of Organic Chemistry, Technical University)

  • Hans E. Krokan

    (Norwegian University of Science and Technology)

  • Finn Kirpekar

    (University of Southern Denmark)

  • Arne Klungland

    (Centre for Molecular Biology and Neuroscience, Institute of Medical Microbiology, Oslo University Hospital
    Institute of Basic Medical Sciences, University of Oslo, PO Box 1018 Blindern, Oslo 0315, Norway.)

  • Pål Ø. Falnes

    (University of Oslo, PO Box 1041 Blindern, Oslo 0316, Norway.
    Centre for Molecular Biology and Neuroscience, Institute of Medical Microbiology, Oslo University Hospital)

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 (mcm5U) from its precursor 5-carboxymethyluridine (cm5U). In this study, we report that (R)- and (S)-5-methoxycarbonylhydroxymethyluridine (mchm5U), hydroxylated forms of mcm5U, are present in mammalian , and , 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 mchm5U are generated from mcm5U, and that the AlkB domain of ALKBH8 specifically hydroxylates mcm5U into (S)-mchm5U in . 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.

Suggested Citation

  • Erwin van den Born & 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, 2011. "ALKBH8-mediated formation of a novel diastereomeric pair of wobble nucleosides in mammalian tRNA," Nature Communications, Nature, vol. 2(1), pages 1-7, September.
    • Handle: RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1173
    DOI: 10.1038/ncomms1173
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