Structure of mouse metallothionein-I gene and its mRNA

Abstract

Metallothioneins are small cysteine-rich proteins that bind heavy metals such as zinc, cadmium, copper and mercury^1,2. Recent interest in these proteins has focused on the part they play in zinc metabolism and heavy metal detoxification¹. Our interest in metallothionein genes stems largely from the observations that these proteins are inducible by both heavy metals and glucocorticoid hormones^1,3. To explore the regulation of these genes, we have isolated cDNA and genomic clones corresponding to mouse metallothionein-I (MT-I)⁴, and have used them to show that both inducers act at the transcriptional level in vivo and in a wide variety of cell lines^5–8. We have also shown that the MT-I gene is amplified during selection for cadmium resistance⁵. To investigate the mechanisms of gene regulation, knowledge of the primary DNA sequence is necessary. Here we present the entire sequence of mouse MT-I gene along with ∼300 bases of 5′ flanking region that presumably includes promoter and regulatory sites. The 5′ mRNA sequence, defined by S₁ nuclease mapping, was combined with sequences of the coding and 3′ untranslated regions obtained previously⁴ to allow a computer prediction of the most stable secondary structure of MT-I mRNA.