Characterization of a putative murine mitochondrial transporter homology of hMRS3/4

We report here a novel murine gene, Mrs3/4, encoding a putative mitochondrial transporter homologous to the yeast mitochondrial RNA splicing protein 3 and 4 (yMRS3&4) and its human counterpart hMRS3/4. By analyses of radiation hybrids, Mrs3/4 was mapped to mouse Chromosome (Chr) 19 between D19Mit66 and D19Mit24 with a distance of 22.4 cR to D19Mit66, a region that is syntenic to human Chromosome 10q24, where the human gene is located. Structural analysis shows that these proteins belong to the mitochondrial carrier family (MCF), which is characterized by three repeats with two transmembrane domains in each repeat. The murine Mrs3/4 gene has two splicing forms similar to the human homolog. The long form corresponds to the 341-amino acid (aa) protein with six transmembrane domains, and the short form corresponds to the 177-aa protein with three transmembrane domains. Both forms have well-conserved signature sequences of MCF. Targeting experiments showed that both forms have mitochondrial localization. Northern blot analyses showed that Mrs3/4 is ubiquitously expressed as a 1.8-kb transcript with a relative abundance in the heart, liver, kidney, and testis. In conclusion, the reported Mrs3/4 gene shows a strong conservation, mitochondrial protein localization, and a ubiquitous expression, which suggests that it has an important role in mammalian cells, most likely as an ion transporter across the mitochondrial inner membrane.