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tRNA N(3)-cytidine methyltransferase METTL8, mitochondrial (METTL8) is a nuclear-encoded mitochondrial matrix enzyme that catalyzes the formation of 3-methylcytidine (m^3^C) at position 32 of specific mitochondrial tRNAs, notably mitochondrial tRNA^Thr^ and tRNA^Ser(UCN)^[1][2][3][4]. METTL8 recognizes these tRNAs through sequence-specific elements in their anticodon stem-loops and requires the presence of certain nucleotide modifications at position 37 as specificity determinants[2][4]. The m^3^C modification introduced by METTL8 is critical for proper tRNA structure and optimal mitochondrial translation[1][2]. Loss of METTL8 results in reduced m^3^C levels, impaired tRNA folding, and mild mitochondrial translation defects, but is not known to directly cause disease or to be a therapeutic drug target based on current evidence[1][2].
Transfer of a methyl group to the N3 position of cytidine at position 32 of mitochondrial tRNA^Thr^ and tRNA^Ser(UCN)^, forming the 3-methylcytidine (m^3^C) modification[1][2][3][4].
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