Regulation of Expression of the Human MTH1 Gene Encoding 8-Oxo-dGTPase
ALTERNATIVE SPLICING OF TRANSCRIPTION PRODUCTS*
- From the ‡Department of Biochemistry, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-82, Japan and the §Department of Biology, Fukuoka Dental College, Fukuoka 814-01, Japan
Abstract
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 MTH1gene encoding 8-oxo-dGTPase. Large amounts ofMTH1 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 ofMTH1 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 MTH1transcript. Allele frequency of this polymorphism is about 20% among healthy volunteers.
Footnotes
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↵* This work was supported by grants from the Ministry of Education, Science, Sports and Culture of Japan and funding from the Human Frontier Science Program.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The nucleotide sequences reported in this paper have been submitted to DDBJ (DNA Data Bank of Japan) under accession numbersD38591 and D38592.
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↵¶ To whom correspondence should be addressed: Fukuoka Dental College, 2-15-1, Tamura, Sawara-ku, Fukuoka 814-01, Japan. Tel.: 81-92-801-0411 (ext. 310); Fax: 81-92-801-4909; E-mail: sekim1{at}college.fdcnet.ac.jp.
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↵1 The abbreviations used are: 8-oxoguanine, 8-oxo-7,8-dihydroguanine; 8-oxo-dGTP, 8-oxo-7,8-dihydro-2′-deoxyguanosine 5′-triphosphate; bp, base pair(s); PBL, peripheral blood lymphocytes; PAGE, polyacrylamide gel electrophoresis; SLIC, single-strand ligation to ss-cDNA; ss, single-strand; RT, reverse transcriptase; MOPS, 4-morpholinepropanesulfonic acid.
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↵2 H. Oda, Y. Nakabeppu, and M. Sekiguchi, unpublished data.
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- Received February 10, 1997.
- Revision received May 8, 1997.
