A single mouse glutathione synthetase gene encodes six mRNAs with different 5' ends

Zheng-Zheng Shi, Bing Z. Carter, Geetha M. Habib, Xiangwei He, Shelley Sazer, Russell M. Lebovitz, Michael W. Lieberman

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

To understand more about the role of glutathione (GSH) in metabolism, we have cloned both cDNA and genomic sequences for mouse glutathione synthetase (GSH syn), the enzyme that catalyzes the last step in the synthesis of glutathione. The mouse cDNA contains an open reading frame (ORF) of 474 aa and shares 64 and 95% deduced amino acid sequence identity with Xenopus cDNA and rat cDNA, respectively. The cDNA complements Schizosaccaromyces pombe strains deficient in GSH syn. The gene is a single-copy gene spanning ~30 kb and is composed of at least 15 exons. Steady-state RNA levels and enzyme activity levels are highest in kidney, about 3-fold lower in liver, and 8- to 10-fold lower in lung and brain. We have identified six different GSH syn RNAs: three, termed types A1, A2, and A3, have different 5' ends that localize to different sites in the gene, but appear to encode the same protein (474 aa). Types B, C1, and C2 all have unique 5' ends and type- specific ORFs, which are shorter than that for types A1, A2, and A3. In liver only type A1 GSH syn RNA is detectable, while in kidney 90% of GSH syn RNA is type A1 and types B and C account for about 10%.

Original languageEnglish (US)
Pages (from-to)215-224
Number of pages10
JournalArchives of Biochemistry and Biophysics
Volume331
Issue number2
DOIs
StatePublished - Jul 15 1996

Keywords

  • cDNA cloning
  • gene structure
  • glutathione synthetase
  • RNA splicing

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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