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- W2610162195 abstract "ALKBH1 is a 2-oxoglutarate- and Fe2+-dependent dioxygenase responsible for multiple cellular functions. Here, we show that ALKBH1 is involved in biogenesis of 5-hydroxymethyl-2΄-O-methylcytidine (hm5Cm) and 5-formyl-2΄-O-methylcytidine (f5Cm) at the first position (position 34) of anticodon in cytoplasmic tRNALeu, as well as f5C at the same position in mitochondrial tRNAMet. Because f5C34 of mitochondrial tRNAMet is essential for translation of AUA, a non-universal codon in mammalian mitochondria, ALKBH1-knockout cells exhibited a strong reduction in mitochondrial translation and reduced respiratory complex activities, indicating that f5C34 formation mediated by ALKBH1 is required for efficient mitochondrial functions. We reconstituted formation of f5C34 on mitochondrial tRNAMetin vitro, and found that ALKBH1 first hydroxylated m5C34 to form hm5C34, and then oxidized hm5C34 to form f5C34. Moreover, we found that the frequency of 1-methyladenosine (m1A) in two mitochondrial tRNAs increased in ALKBH1-knockout cells, indicating that ALKBH1 also has demethylation activity toward m1A in mt-tRNAs. Based on these results, we conclude that nuclear and mitochondrial ALKBH1 play distinct roles in tRNA modification." @default.
- W2610162195 created "2017-05-12" @default.
- W2610162195 creator A5001653266 @default.
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- W2610162195 creator A5075941948 @default.
- W2610162195 date "2017-05-02" @default.
- W2610162195 modified "2023-10-18" @default.
- W2610162195 title "ALKBH1 is an RNA dioxygenase responsible for cytoplasmic and mitochondrial tRNA modifications" @default.
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- W2610162195 doi "https://doi.org/10.1093/nar/gkx354" @default.
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