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tRNA N

Definition:

Mitochondrial S-adenosyl-L-methionine-dependent methyltransferase that mediates N(3)-methylcytidine modification of residue 32 of the tRNA anticodon loop of mitochondrial tRNA(Ser)(UCN) and tRNA(Thr). N(3)-methylcytidine methylation modification regulates mitochondrial translation efficiency and is required for activity of the respiratory chain. N(3)-methylcytidine methylation of mitochondrial tRNA(Ser)(UCN) requires the formation of N(6)-dimethylallyladenosine(37) (i6A37) by TRIT1 as prerequisite. May also mediate N(3)-methylcytidine modification of mRNAs. The existence of N(3)-methylcytidine modification on mRNAs is however unclear, and additional evidences are required to confirm the role of the N(3)-methylcytidine-specific mRNA methyltransferase activity of METTL8 in vivo.

References:

[1]. Ran Chen, et al. Crystal structure of human METTL6, the m3C methyltransferase. Commun Biol. 2021 Dec 3;4(1):1361. [Content Brief]

[2]. Jia Cui, et al. Nucleotide resolution profiling of m3C RNA modification by HAC-seq. Nucleic Acids Res. 2021 Mar 18;49(5):e27. [Content Brief]

[3]. Shibiao Li, et al. Structural basis for METTL6-mediated m3C RNA methylation. Biochem Biophys Res Commun. 2022 Jan 22;589:159-164. [Content Brief]

[4]. Valentina V Ignatova, et al. METTL6 is a tRNA m3C methyltransferase that regulates pluripotency and tumor cell growth. Sci Adv. 2020 Aug 26;6(35):eaaz4551. [Content Brief]

[5]. Luang Xu, et al. Three distinct 3-methylcytidine (m3C) methyltransferases modify tRNA and mRNA in mice and humans. J Biol Chem. 2017 Sep 1;292(35):14695-14703. [Content Brief]

[6]. Xue-Ling Mao, et al. Mutually exclusive substrate selection strategy by human m3C RNA transferases METTL2A and METTL6. Nucleic Acids Res. 2021 Aug 20;49(14):8309-8323. [Content Brief]

[7]. Eva Schöller, et al. Balancing of mitochondrial translation through METTL8-mediated m3C modification of mitochondrial tRNAs. Mol Cell. 2021 Dec 2;81(23):4810-4825.e12. [Content Brief]

[8]. Nicole Kleiber, et al. The RNA methyltransferase METTL8 installs m3C32 in mitochondrial tRNAsThr/Ser(UCN) to optimise tRNA structure and mitochondrial translation. Nat Commun. 2022 Jan 11;13(1):209. [Content Brief]

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