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

被引:136
作者
van den Born, Erwin [2 ]
Vagbo, Cathrine B. [3 ]
Songe-Moller, Lene [1 ]
Leihne, Vibeke [2 ]
Lien, Guro F. [1 ]
Leszczynska, Grazyna [4 ]
Malkiewicz, Andrzej [4 ]
Krokan, Hans E. [3 ]
Kirpekar, Finn [5 ]
Klungland, Arne [1 ,6 ]
Falnes, Pal O. [1 ,2 ]
机构
[1] Oslo Univ Hosp, Ctr Mol Biol & Neurosci, Inst Med Microbiol, Dept Mol Microbiol, Oslo, Norway
[2] Univ Oslo, Dept Mol Biosci, N-0316 Oslo, Norway
[3] Norwegian Univ Sci & Technol, Dept Canc Res & Mol Med, N-7489 Trondheim, Norway
[4] Tech Univ Lodz, Inst Organ Chem, PL-90924 Lodz, Poland
[5] Univ So Denmark, Dept Biochem & Mol Biol, DK-5230 Odense M, Denmark
[6] Univ Oslo, Inst Basic Med Sci, N-0315 Oslo, Norway
来源
NATURE COMMUNICATIONS | 2011年 / 2卷
关键词
MALDI MASS-SPECTROMETRY; DNA-DAMAGE; OXIDATIVE DEMETHYLATION; ALKYLATION DAMAGE; METHYLTRANSFERASE; REPAIR; CONVERSION; POSITION; GENOME; DOMAIN;
D O I
10.1038/ncomms1173
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:7
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