Genomic organization, physical mapping, and expression analysis of the human protein arginine methyltransferase 1 gene

Protein arginine methyltransferases (PRMTs) regulate mRNA processing and maturation by modulating the activity of RNA-binding proteins through methylation. The cDNA for human PRMT1 (HRMT1L2) was recently identified. In this paper, we describe the complete genomic organization of the human PRMT1 gene (GenBank Accession No. AF222689), together with its precise chromosomal localization in relation to other neighboring genes. We have also examined its expression in a total RNA panel of 26 human tissues, the BT-474 breast carcinoma cell line, and 16 breast tumors. PRMT1, which spans 11.2 kb of genomic sequence on chromosome 19q13.3, is located in close proximity to the IRF3 and RRAS genes and is transcribed in the opposite direction. It is formed of 12 coding exons and 11 intervening introns, and shows structural similarity to other PRMT genes. Three PRMT1 isoforms exist as a result of alternative mRNA splicing, Amino acid sequence comparison of the splicing variants indicates that they are all enzymatically active methyl transferases, but with different N-terminal hydrophobic regions. PRMT1 expression was detected in a variety of tissues. We have shown that the relative prevalence of alternatively spliced forms of PRMT1 is different between normal and cancerous breast tissues. Although PRMT1 was not found to be hormonally regulated by steroid hormones in breast cancer cells, our results suggest that two variants of PRMT1 are down regulated in breast cancer. (C) 2000 Academic Press.