Characterization of the human mitochondrial ribosomal S12 gene

Translation of mitochondrial encoded mRNAs occurs on mitochondrial ribosomes. The ribosomal RNA components of the mitochondrial ribosomes are coded for by mitochondrial DNA, while all the protein subunits are coded for by nuclear chromosomes. The only mitochondrial protein subunit cloned in mammals is MRPL12, making the study of the role of mitochondrial translation in human disease difficult. We have now cloned the gene for the human mitochondrial ribosomal protein S12, termed RPMS12, based on its homology to the Drosophila tko gene. The gene stretches over 1.7 kb of genomic DNA and maps to chromosome 19q13, near marker D19S881. The mRNA shows three distinct patterns of splicing within the 5' untranslated region in all tissues examined, one form being predominant over the other two. The coding region of the leader sequence is interrupted in codon 17 by a second intron of 990 bases. The mRNA is predicted to be translated to a prepeptide of 138 amino acids in length and processed to a peptide of 112 aa and a molecular mass of 12.3 kDa. The protein is very basic, with a predicted pI of 10.3, and is highly conserved through evolution. The functional role and map location of the gene make it a candidate gene for susceptibility to aminoglycoside ototoxicity and for the autosomal dominant deafness gene DFNA4.