METTL15 interacts with the assembly intermediate of murine mitochondria! small ribosomal subunit to form m4OC840 12S rRNA residue

Mammalian mitochondrial ribosomes contain a set of modified nucleotides, which is distinct from that of the cytosolic ribosomes. Nucleotide m(4)C840 of the murine mitochondrial 12S rRNA is equivalent to the dimethylated m(4)Cm1402 residue of Escherichia coil 16S rRNA. Here we demonstrate that mouse METTL15 protein is responsible for the formation of m(4)C residue of the 12S rRNA. Inactivation of Met1115 gene in murine cell line perturbs the composition of mitochondrial protein biosynthesis machinery. Identification of METTL15 interaction partners revealed that the likely substrate for this RNA methyltransferase is an assembly intermediate of the mitochondrial small ribosomal subunit containing an assembly factor RBFA.