Journal article
Preferential selection of MnSOD transcripts in proliferating normal and cancer cells
Oncogene, Vol.31(10), pp.1207-1216
03/08/2012
DOI: 10.1038/onc.2011.325
PMCID: PMC3208126
PMID: 21804600
Abstract
Manganese superoxide dismutase (MnSOD) is a nuclear encoded and mitochondrial matrix localized redox enzyme that is known to regulate cellular redox environment. 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 1.5 kb
MnSOD
transcript levels was observed in quiescent cells, while the abundance of the longer transcript showed a direct correlation with the percentage of S-phase cells. Log transformed expression ratio of the longer to 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 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.
Details
- Title: Subtitle
- Preferential selection of MnSOD transcripts in proliferating normal and cancer cells
- Creators
- Leena Chaudhuri - Division of Hematology and Oncology, Mayo Clinic, Scottsdale, Arizona, USAAdam M Nicholson - Free Radical and Radiation Biology Division, Department of Radiation Oncology, The University of Iowa, Iowa City, Iowa, USAAmanda L Kalen - Free Radical and Radiation Biology Division, Department of Radiation Oncology, The University of Iowa, Iowa City, Iowa, USAPrabhat C Goswami - Free Radical and Radiation Biology Division, Department of Radiation Oncology, The University of Iowa, Iowa City, Iowa, USA
- Resource Type
- Journal article
- Publication Details
- Oncogene, Vol.31(10), pp.1207-1216
- DOI
- 10.1038/onc.2011.325
- PMID
- 21804600
- PMCID
- PMC3208126
- ISSN
- 0950-9232
- eISSN
- 1476-5594
- Language
- English
- Date published
- 03/08/2012
- Academic Unit
- Radiation Oncology; Iowa Superfund Research Program
- Record Identifier
- 9984047791602771
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