METAZOAN NUCLEAR GENES FOR MITORIBOSOMAL PROTEIN S12

We have characterized nuclear genes for mitoribosomal protein S12 (mt- rps12) a major component of the ribosomal accuracy centre, in human, m ouse and Drosophila melanogaster. In human and Drosophila, and probabl y also in mouse, there is a single intron within the coding region, lo cated in the mitochondrial targeting pre-sequence. In humans, the mRNA structure is highly suggestive of translational regulation. In all th ree species, there is an amino-acid substitution with respect to eubac terial homologues in a residue implicated in aminoglycoside resistance . The only viable mutant allele of the Drosophila gene, associated wit h a bang-sensitive phenotype (paralysis upon mechanical vibration, ari sing from a mechanoreceptor cell defect) also has a novel substitution in a conserved region implicated in translational fidelity. Given the involvement of the mitoribosomal accuracy centre in human sensorineur al deafness by virtue of rRNA mutations, our results indicate that thi s fly mutant may be a useful animal model of this disorder, and earmar k the gene for mt-rps12 as a candidate in human hearing impairment. (C ) 1997 Elsevier Science B.V.