The 3 ' UTR of human MnSOD mRNA hybridizes to a small cytoplasmic RNA and inhibits gene expression

Human MnSOD localizes to the mitochondria and plays a key protective role b y detoxifying oxygen free radicals. The MnSOD mRNA 3' UTR contains a 280-bp region (Alu-like element or Alu-E) that shows high homology to human Alu a nd 7SL sequences. MnSOD 3' UTR probes hybridize to a specific cytoplasmic R NA species of similar to 300 nucleotides. This antisense RNA is most Likely 7SL RNA based on its size, ubiquitousness, high levels, and lack of induci bility, Hybridization of this small RNA to the MnSOD 3' UTR may modulate po sttranscriptional MnSOD gene expression. This regulation could occur by sev eral means including inhibition of translation and mRNA destabilization, Re gulation at the level of translational initiation does not seem to occur as MnSOD mRNA containing the Alu-E is efficiently bound by ribosomes, To test the role of the MnSOD 3' UTR, and in particular the Alu-E in gene expressi on, luciferase reporter gene constructs were made containing various region s of the MnSOD 3' UTR including the Alu-E, These constructs were transfecte d into human A549 lung carcinoma cells and luciferase activity was measured . Reporter constructs containing the MnSOD 3' UTR and the Alu-E repress luc iferase activity. Taken together, these results suggest that naturally occu rring antisense RNA may bind MnSOD mRNA and repress its expression. These r esults also suggest that other mRNAs containing Alu elements may be similar ly repressed, (C) 2000 Academic Press.