HUMAN THERMOLABILE PHENOL SULFOTRANSFERASE GENE (STM) - MOLECULAR-CLONING AND STRUCTURAL CHARACTERIZATION

Thermolabile (TL) phenol sulfotransferase (PST) catalyzes the sulfate conjugation of phenolic monoamines such as dopamine. The level of acti vity of TL PST in at least one human tissue, the blood platelet, is co ntrolled by a genetic polymorphism. We previously cloned and expressed a cDNA for human liver TL PST and localized its gene, STM, to human c hromosome 16p11.2, a region of the chromosome to which the Batten dise ase gene is also localized. A cDNA for human brain TL PST with an iden tical open reading frame (ORF) has also been cloned. We have now isola ted the human TL PST gene, STM, and have characterized its structural organization as an additional step toward understanding molecular mech anisms involved in the regulation of levels of TL PST activity in huma n tissue. STM consists of ten exons and nine introns, with a total len gth of approximately 8.4 kb. Exons range from 88-499 bp in length, whi le introns vary from 89-1855 bp. Many of the exon-intron splice juncti ons in STM are located at positions identical to those of splice junct ions in the human dehydroepiandrosterone (DHEA) ST gene, STD, and the rat phenol or aryl ST gene. The first two STM exons are represented in the 5'-UTR of a longer TL PST cDNA expressed in both brain and liver, while exon III is represented in a shorter cDNA 5'-UTR expressed in b oth tissues. These observations suggest alternative transcription init iation and/or alternative splicing as explanations for the existence o f TL PST mRNA species with two different 5'-UTRs. 5 '-Flanking region( s) of STM contained neither canonical TATA nor CCAAT elements, but the y did contain pyrimidine-rich stretches. Northern blot analyses showed that an mRNA species approximately 1.4 kb in length was expressed in human liver, kidney, lung, small intestine, spleen and leukocyte. Mole cular cloning and structural characterization of STM will make it poss ible to study molecular genetic mechanisms involved in the regulation of TL PST activity in human tissue. (C) 1995 Academic Press, Inc.