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-dGTPase) hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP, thereby preventing misincorporation of 8-oxo-dGTP into DNA. We investigated expression of MTH1 gene encoding 8-oxo-dGTPase. Large amounts of MTH1 mRNA were present in thymus and testis, embryonic tissues, and certain cell lines. In peripheral blood lymphocytes, the level of MTH1 mRNA was significantly increased after concomitant treatment with phytohemagglutinin and interleukin-2. Analyses of the 5' regions of the MTH1 transcripts revealed that 7 types of MTH1 mRNAs, which may be produced by transcription initiation at different sites and/or alternative splicing. The MTH1 gene consists of 5 major exons, some of which are composed of differentially processed segments. All types of MTH1 mRNAs carry the entire coding region, and may be functional. Three ATG initiation codons in-frame were found in the 5' regions of some of the MTH1 mRNAs. There is a polymorphic alteration at the 5' splicing site (GT to GC) located in exon 2, an event which affects splicing patterns of the MTH1 transcript. Allele frequency of this polymorphism is about 20% among healthy volunteers.
Oda
H
H
Department of Biochemistry, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-82, Japan.
Nakabeppu
Y
Y
Furuichi
M
M
Sekiguchi
M
M
D017398:Alternative Splicing / Q000235:genetics*; D001483:Base Sequence; D003001:Cloning, Molecular; D017931:DNA Primers / Q000378:metabolism; D045643:DNA Repair Enzymes; D015870:Gene Expression; D006801:Humans; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic
D017931:DNA Primers; D012333:RNA, Messenger; D010744:Phosphoric Monoester Hydrolases; C078207:8-oxodGTPase; D045643:DNA Repair Enzymes