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Preferential selection of MnSOD transcripts in proliferating normal and cancer cells
L Chaudhuri1, A M Nicholson, A L Kalen
1Division of Hematology and Oncology, Mayo Clinic, Scottsdale, AZ, USA.
Oncogene
|August 2, 2011
Summary
The 3'-untranslated region (UTR) of manganese superoxide dismutase (MnSOD) regulates its expression. MnSOD UTR controls MnSOD levels during cell growth and in response to radiation, impacting cellular redox balance.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Manganese superoxide dismutase (MnSOD) is a key redox enzyme regulating cellular redox environment.
- Cellular redox status shifts during quiescent and proliferative cell cycle transitions.
- Human MnSOD exists as two transcripts (1.5 and 4.2 kb) due to alternative polyadenylation.
Purpose of the Study:
- Investigate the role of MnSOD 3"-untranslated region (UTR) in regulating MnSOD expression.
- Determine MnSOD regulation during quiescent/proliferative cycles and in response to radiation.
Main Methods:
- Analysis of MnSOD transcript levels in different cell states.
- Reporter assays to assess 3"-UTR activity.
- Deletion analysis of AU-rich elements within the 3"-UTR.
Main Results:
- The 1.5-kb MnSOD transcript increased in quiescent cells; the 4.2-kb transcript correlated with S-phase percentage.
- AU-rich elements in the longer 3"-UTR decreased reporter activity.
- Overexpression of the longer 3"-UTR increased MnSOD mRNA and protein, reducing S-phase cells.
- Irradiation elevated the 1.5-kb transcript and increased reporter activity for the shorter 3"-UTR construct.
Conclusions:
- The MnSOD 3"-UTR plays a regulatory role in MnSOD expression.
- Differential regulation occurs in response to cellular growth states and radiation exposure.
- MnSOD 3"-UTR isoforms influence cellular redox homeostasis and proliferation.
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