Structure of primate and rodent orthologs of the prostate cancer susceptibility gene ELAC2.

The human ELAC2 gene was the first candidate prostate cancer susceptibility gene identified by linkage analysis and positional cloning. DNA sequence indicates a protein of 826 amino acids encoded by 24 exons. In the present study, we characterized the coding sequence of chimpanzee and gorilla ELAC2 orthologs by direct sequencing of genomic fragments, and of cynomolgus monkey and rat orthologs by screening cDNA libraries. The orthologs characterized in the chimpanzee, gorilla and cynomolgus monkey also encode proteins of 826 amino acids, sharing 98.9%, 98.5% and 93.7% sequence identity with the human protein. Our analyses of the mouse ELAC2 gene identified two alternative mRNA transcripts. One is translated into a protein of 824 a.a. (mouse ELAC2), whereas the other one encodes a protein of 831 amino acids (mouse ELAC2A) resulting from an alternatively spliced form of 25 exons. The rat ELAC2 gene ortholog also expressed two similar alternatively spliced transcripts. These two forms are ubiquitously expressed in mouse and rat tissues. The highest levels of expression of the ELAC2 form are observed in the testis while the lowest levels are seen in the prostate and in the muscle. However, it is of interest to note that the relative abundance of the rat and mouse ELAC2 transcripts, measured by real-time quantitative PCR, is higher than the respective ELAC2A forms in all surveyed tissues except for the prostate and the muscle. The ELAC2A transcript levels are 4.1 to 5.0-fold higher than the ELAC2 levels in the prostate of rat and mouse, respectively. A fine analysis of the conserved domains on the primary structure of ELAC2 orthologs revealed the presence of a putative beta-CASP domain shared by the PSO2 (SNM1) DNA interstrand cross-link repair proteins, and the 73-kDa subunit of mRNA 3' end cleavage and polyadenylation specificity factor (CPSF73) as well as Artemis proteins, thus suggesting a potential interaction of ELAC2 gene product with nucleic acids and more specifically with RNA targets. Taken together, these data offer useful tools to further study the regulation and cellular function of ELAC2 gene in experimental models and provide further insight concerning conserved amino acid motifs that could have biological significance.