REGULATION OF EXPRESSION OF THE HUMAN MTH1 GENE ENCODING 8-OXO-DGTPASE - ALTERNATIVE SPLICING OF TRANSCRIPTION PRODUCTS

The enzyme 8-oxo-7,8-dihydrodeoxyguanosine triphosphatase (8-oxo-dGTPa se) hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP, thereby preventing misincorpo ration of 8-oxo-dGTP into DNA. We investigated expression of MTH1 gene encoding 8-oxo-dGTPase. Large amounts of MTH1 mRNA were present in th ymus and testis, embryonic tissues, and certain cell lines. In periphe ral blood lymphocytes, the level of MTH1 mRNA was significantly increa sed after concomitant treatment with phytohemagglutinin and interleuki n-a. Analyses of the 5' regions of the MTH1 transcripts revealed that 7 types of MTH1 mRNAs, which may be produced by transcription initiati on at different sites and/or alternative splicing. The MTH1 gene consi sts of 5 major exons, some of which are composed of differentially pro cessed segments. All types of MTH1 mRNAs carry the entire coding regio n, and may be functional. Three ATG initiation codons in-frame were fo und in the 5' regions of some of the MTH1 mRNAs, There is a polymorphi c alteration at the 5' splicing site (GT to GC) located in exon 2, an event which affects splicing patterns of the MTH1 transcript. Allele f requency of this polymorphism is about 20% among healthy volunteers.