Differential induction and decay of manganese superoxide dismutase mRNAs

Human manganese superoxide dismutase (MnSOD) is encoded by two mRNAs of 4 and 1 kb, respectively. These mRNAs are transcribed from the same gene and have an identical coding sequence, but differ in the 3′ untranslated sequence because of alternate polyadenylation. Tumor necrosis factor-α (TNF) induced both 4- and 1-kb mRNAs in all the human cell lines examined. However, the relative expression of these mRNAs varied significantly among different cell lines after an 8-h treatment with TNF. Therefore, the time course of induction by TNF and the decay of MnSOD mRNAs after TNF removal were analyzed. The rate of accumulation of the 4-kb mRNA was initially much greater than that of the 1-kb mRNA, suggesting that the 4-kb mRNA was produced faster than the -kb mRNA. The rapid accumulation of the 4-kb mRNA was offset after a few hours by an enhanced rate of decay. The half-life of the 4-kb mRNA was ∼2-4 h in different cells while that of the 1-kb mRNA was ∼10-12 h. This different half-life of mRNAs that encode the same protein suggests that their relative expression is also regulated by a post-transcriptional mechanism affecting their turnover. Additional evidence supporting the differential decay of the two MnSOD mRNAs was obtained by incubation in a rabbit reticulocyte cell-free system; the 4-kb mRNA decayed rapidly while the 1-kb mRNA appeared to be stable.