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-alpha (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 1-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 approximately 2-4 h in different cells while that of the 1-kb mRNA was approximately 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.
Melendez
J A
JA
Department of Biological Sciences, State University of New York, Albany 12222.
Baglioni
C
C
D000818:Animals; D002460:Cell Line; D002474:Cell-Free System; D005609:Free Radicals / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D012156:Reticulocytes / Q000187:drug effects / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D005609:Free Radicals; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013482:Superoxide Dismutase