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

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

van den Born E,Vågbø CB,Songe-Møller L,Leihne V,Lien GF,Leszczynska G,Malkiewicz A,Krokan HE,Kirpekar F,Klungland A,Falnes PØ

doi

10.1038/ncomms1173

subject

Has Abstract

pub_date

2011-02-01 00:00:00

pages

172

issn

2041-1723

pii

ncomms1173

journal_volume

2

pub_type

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