CHAPTER 10: Role of ALKBH8 in the Synthesis of Wobble Uridine Modifications in tRNA

Human ALKBH8 is one of nine AlkB homologues (ALKBHs) related to the Escherichia coli AlkB protein, a 2-oxoglutarate- and Fe(ii)-dependent oxygenase that catalyses the hydroxylation of damaging methyl groups in DNA leading to their spontaneous release. ALKBH8 was recently shown to be a bifunctional tRNA modification enzyme, carrying both oxygenase and methyltransferase activities, and is involved in the formation of specific modified uridines found on the wobble position of tRNAs. Here, we describe the discovery of the ALKBH8 function and we elaborate on the presence of ALKBH8 homologues in other organisms. The possible functional and regulatory roles of ALKBH8-mediated tRNA modification are discussed.