Cellular redox environment changes during transitions between quiescent and proliferative cycles.
Human MnSOD has two poly(A) sites resulting in two transcripts: 1.5 and 4.2 kb. The present study investigates if the 3'-untranslated region (UTR) of MnSOD regulates its expression during transitions between quiescent and proliferating cycles, and in response to radiation. A preferential increase in the levels of the 1.5-kb MnSOD transcript was observed in quiescent cells, whereas the abundance of the longer transcript showed a direct correlation with the percentage of S-phase cells.
The log-transformed expression ratio of the longer to the shorter transcript was also higher in proliferating normal and cancer cells.
Deletion and reporter assays showed a significant decrease in reporter activity in constructs carrying multiple AU-rich sequence that are present in the 3'-UTR of the longer MnSOD transcript.
Overexpression of the MnSOD 3'-UTR representing the longer transcript enhanced endogenous MnSOD mRNA levels, which was associated with an increase in MnSOD protein levels and a decrease in the percentage of S-phase cells.
Irradiation increases the mRNA levels of the 1.5-kb MnSOD transcript, which was consistent with a significant increase in the reporter activity of the construct carrying the 3'-UTR of the shorter transcript.
We conclude that the 3'-UTR of MnSOD regulates MnSOD expression in response to different growth states and radiation.