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

Protein arginine methyltransferases (PRMTs) regulate mRNA processing and ma turation by modulating the activity of RNA-binding proteins through methyla tion. The cDNA for human PRMT1 (HRMT1L2) was recently identified. In this p aper, we describe the complete genomic organization of the human PRMT1 gene (GenBank Accession No. AF222689), together with its precise chromosomal lo calization in relation to other neighboring genes. We have also examined it s expression in a total RNA panel of 26 human tissues, the BT-474 breast ca rcinoma cell line, and 16 breast tumors. PRMT1, which spans 11.2 kb of geno mic sequence on chromosome 19q13.3, is located in close proximity to the IR F3 and RRAS genes and is transcribed in the opposite direction. It is forme d of 12 coding exons and 11 intervening introns, and shows structural simil arity to other PRMT genes. Three PRMT1 isoforms exist as a result of altern ative mRNA splicing, Amino acid sequence comparison of the splicing variant s indicates that they are all enzymatically active methyl transferases, but with different N-terminal hydrophobic regions. PRMT1 expression was detect ed in a variety of tissues. We have shown that the relative prevalence of a lternatively spliced forms of PRMT1 is different between normal and cancero us breast tissues. Although PRMT1 was not found to be hormonally regulated by steroid hormones in breast cancer cells, our results suggest that two va riants of PRMT1 are down regulated in breast cancer. (C) 2000 Academic Pres s.