ABH8

ABH8, the protein encoded by the ALKBH8 gene, modifies tRNAs by methylating their anticodon wobble uridine residues. The variations in the ALKBH8 gene are associated with the "intellectual developmental disorder, autosomal recessive type 71" (MIM: 618504) phenotype in the OMIM database. This phenotype is characterized by global developmental delay, facial dysmorphic features, and psychiatric problems. To date, 12 patients from five distinct families carrying variants of the ALKBH8 gene have been reported in the literature...

The Escherichia coli DNA repair enzyme AlkB is a 2-oxoglutarate (2OG)-dependent Fe(2+) binding dioxygenase that removes methyl lesions from DNA and RNA. To date, nine human AlkB homologues are known: ABH1 to ABH8 and the obesity-related FTO. Similar to AlkB, these homologues exert their activity on nucleic acids, although for some homologues the biological substrate remains to be identified. 2OG dioxygenases require binding of the cofactors Fe(2+) and 2OG in the active site to form a catalytically competent complex...

Humans express nine paralogs of the bacterial DNA repair enzyme AlkB, an iron/2-oxoglutarate-dependent dioxygenase that reverses alkylation damage to nucleobases. The biochemical and physiological roles of these paralogs remain largely uncharacterized, hampering insight into the evolutionary expansion of the AlkB family. However, AlkB homolog 8 (ABH8), which contains RNA recognition motif (RRM) and methyltransferase domains flanking its AlkB domain, recently was demonstrated to hypermodify the anticodon loops in some tRNAs...

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tRNA nucleosides are extensively modified to ensure their proper function in translation. However, many of the enzymes responsible for tRNA modifications in mammals await identification. Here, we show that human AlkB homolog 8 (ABH8) catalyzes tRNA methylation to generate 5-methylcarboxymethyl uridine (mcm(5)U) at the wobble position of certain tRNAs, a critical anticodon loop modification linked to DNA damage survival. We find that ABH8 interacts specifically with tRNAs containing mcm(5)U and that purified ABH8 complexes methylate RNA in vitro...