AlkB homolog 8, tRNA methyltransferase (ALKBH8)

AlkB homolog 8, tRNA methyltransferase (ALKBH8) is an enzyme responsible for the post-transcriptional modification of a specific uridine base at the wobble position (position 34) in the anticodon loop of several tRNAs. ALKBH8 catalyzes methylation to generate 5-methoxycarbonylmethyluridine (mcm5U) and related derivatives, crucial modifications that promote translation accuracy and efficient decoding of mRNA codons[1][2][3][5]. In mammals, ALKBH8-dependent tRNA modifications are important for the synthesis of selenoproteins, including antioxidant enzymes, thereby linking ALKBH8 to redox regulation and responses to oxidative and DNA-damaging stress[3][5][6]. Loss or dysfunction of ALKBH8 results in impaired protein synthesis, increased sensitivity to DNA damage, oxidative stress, and is causally linked to neurodevelopmental and intellectual disability disorders[2][6]. The enzyme contains both a methyltransferase domain unique among AlkB family proteins and a 2-oxoglutarate (2-OG) dependent dioxygenase domain, enabling a unique two-step RNA modification pathway[5]. While not a direct therapeutic target for drugs or inhibitors as of now, its enzymatic activity and the cellular functions it supports make it a focus of interest for disease modeling and biomarker discovery in neurodevelopmental and oxidative stress-related conditions.

Other names

tRNA (carboxymethyluridine(34)-5-O)-methyltransferase ALKBH8ABH8MGC10235TRM9TRMT9AAlkylated DNA repair protein alkB homolog 8Alpha-ketoglutarate-dependent dioxygenase ALKBH8S-adenosyl-L-methionine-dependent tRNA methyltransferase ALKBH8tRNA methyltransferase 9 relatedMRT71TRMT9