Structural and comparative analysis of murine Mtch1 gene family

Abstract

A brain-specific cDNA fragment from mouse was isolated by subtracting brain cDNAs with liver cDNAs. The cDNA fragment was revealed to encode a novel mitochondrial carrier from sequence similarity, named as Mtch1 (mitochondrial carrier homolog 1). The Mtch1 gene was expressed predominately in nervous system of 9.5 dpc mouse embryo and 10.5 dpc embryo and in adult brain, suggesting that the Mtch1 gene influence the early development of brain tissues. Several murine Mtch1 cDNA clones were obtained from brain cDNA library. The sequence analysis of the cDNA clones revealed two Mtch1 transcripts by alternative splicing of 51 bp as confirmed by RT-PCR. Two different putative Mtch1 proteins consist of 372 or 389 amino acids. About 20 Kb of the Mtch1 genomic sequence was assembled by connecting the overlapped sequences of several genomic clones. The gene was compromised of 13 exons and 12 introns with all the splice donor and acceptor sites conforming to the canonical GT/AG rule. The promoter, lacking TATA and CAAT boxes, harbored a CREB and six Sp1 binding sites. A CpG island was found in the promoter and the region surrounding translation start site. Southern blot analysis showed that the Mtch1 gene was single copy. The Mtch1 transcription was mainly initiated at site 118 bp upstream from the translation start codon. The Mtch1 gene was located on human chromosome 6p21 and 15.23 cM of mouse chromosome 17. The Mtch1 orthologs were identified in human, hamster, rat, Drosophila, Caenorhabditis elegans, and Bombyx mori from a comprehensive database analysis. Like murine Mtch1 cDNA, human MTCH1 cDNA potentially encode polypeptides with 372 or 389 and Drosophila mtch and Bombyx mtch were composed of 295 and 316 amino acids, respectively. Murine Mtch2 and its orthologs, the murine Mtch1 paralogs, were found in human, chicken, and zebrafish. The murine Mtch2 cDNA was comprised of an open eading frame of 303 amino acids. Two messages of Mtch2 gene were expressed constitutively...