Regulation of expression of the human MTH1 gene encoding 8-Oxo-dGTPase: Alternative splicing of transcription products

Hisanobu Oda, Yusaku Nakabeppu, Masato Furuichi, Mutsuo Sekiguchi

Research output: Contribution to journalArticle

48 Citations (Scopus)

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 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 inframe 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.

Original languageEnglish
Pages (from-to)17843-17850
Number of pages8
JournalJournal of Biological Chemistry
Volume272
Issue number28
DOIs
Publication statusPublished - Aug 5 1997

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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