Human Cu/Zn superoxide dismutase gene: molecular characterization of its two mRNA species

Abstract

Two cytoplasmic superoxide dismutase (SOD-1) mRNAs of about 0.7 and 0.9 kilobases (Kb.) were previously found in a variety of human cells. The two SOD-1 mRNAs are transcribed from the same gene and the major 0.7 Kb. species is approximately four times more abundant than the minor 0.9 Kb. mRNA. These two mRNAs differ in the length of their 3'-untranslated region and both have multiple 5'-ends. The longer transcript contains 222 additional nucleotides beyond the 3'-polyadenylated terminus of the short mRNA. S1 nuclease mapping and sequence analysis showed that these extra 222 nucleotides are specified by sequences contiguous to those shared by the two SOD-1 mRNAs. The 5'-termini of the two SOD-1 mRNAs were identified and mapped by both primer extension and S1 mapping. The majority of SOD-1 mRNA molecules (90-95%) have a 5'-start site located 23 base pairs (b.p.) downstream of the hexanucleotide -TATAAA-. The rest of the SOD-1 mRNA molecules have 5'-termini 30, 50 and 65 b.p. upstream from the major start region.

Transgenic mice with increased Cu/Zn-superoxide dismutase activity: animal model of dosage effects in Down syndrome.

“…The first is that a locus for familial AD has been identified on chromosome 21 (26). The second is that the gene for the putative precursor of the amyloid ( protein, which is deposited in the neurons and cerebral vessels of individuals with AD, is also on chromosome 21 (27)(28)(29)(30), in the same vicinity as the familial AD locus (26,27 In addition to their relevance to the study of DS and AD, the h-CuZnSOD transgenics will also be of importance in the investigation of the role of CuZnSOD in protection against the adverse effects of a variety of exogenous agents.…”

“…USA 84 (1987) dodecyl sulfate/200 Ag of proteinase K per ml and incubated at 50'C for 12-16 hr. DNA was extracted and analyzed as described (21). DNA (10 ,ug) was digested with either Bgl II or Pst I and blot-hybridized with either a 32P-labeled 1.3-kb HindIII fragment of the h-CuZnSOD gene ( Fig.…”

“…Down syndrome (DS), the phenotypic expression of human trisomy 21 (Ts2l), is manifested by morphogenetic abnormalities, mental retardation, immunological abnormalities, and the pathological manifestations of Alzheimer disease (AD) (1,2). Although the mechanisms by which the presence of an extra chromosome 21 causes developmental and functional abnormalities are largely unknown (1), analyses of the activities or concentrations of the known gene products of this chromosome have revealed the existence of precise gene dosage effects.…”

Renal antioxidant enzyme mRNA levels are increased in rats with experimental diabetes mellitus

“…A 0.45-kilobase (kb) 32 P-labelled antisense Cu,Zn-SOD cRNA was synthesized using a Xho I linearized SP65 vector containing the 450-bp Alu I to Taq I human Cu,Zn-SOD cDNA insert [15], as previously described [16]. A 0.468-kb 32 P-labelled antisense catalase cRNA was synthesized using a Xho I linearized SP65 vector containing the 1250-bp Hind III to Pvu II human catalase cDNA insert [17], as previously described [16].…”

Translation of a Testis-Specific Cu/Zn Superoxide Dismutase (SOD-1) mRNA Is Regulated by a 65-Kilodalton Protein Which Binds to Its 5′ Untranslated Region

“…However, two size classes of SOD-1 mRNAs, which differ by 200 nucleotides in their 3Ј UTRs, have been detected in certain human somatic tissues (61,62). Recently, it has been shown that the longer somatic SOD-1 mRNA produces three times more enzyme when transfected into COS 1 and human 293 cells than the shorter SOD-1 mRNA (36).…”