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Preferential selection of MnSOD transcripts in proliferating normal and cancer cells

Oncogene volume 31, pages 1207–1216 (2012)Cite this article

Abstract

Manganese superoxide dismutase (MnSOD) is a nuclear encoded and mitochondrial matrix-localized redox enzyme that is known to regulate the 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 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.

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Acknowledgements

We thank Dr Ehab H Sarsour and Maneesh G Kumar at the Free Radical and Radiation Biology Division, and Amy Dubinsky and Dr Beverly L Davidson at the Department of Internal Medicine, for technical assistance with the UTR cloning and luciferase reporter assay; Drs Ann Simons and Melissa Fath for human oral squamous and lung cancer cells; Mr Gareth Smith with editorial assistance and the staff at the Flow Cytometry and Radiation and Free Radical Research Core Facilities. Funding from NIH CA111365 and NIEHS P42 ES 013661 supported this work.

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Authors and Affiliations

  1. Division of Hematology and Oncology, Mayo Clinic, Scottsdale, AZ, USA

    L Chaudhuri

  2. Department of Radiation Oncology, Free Radical and Radiation Biology Division, The University of Iowa, Iowa City, IA, USA

    A M Nicholson, A L Kalen & P C Goswami

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  1. L Chaudhuri
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  2. A M Nicholson
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  3. A L Kalen
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  4. P C Goswami
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Correspondence to P C Goswami.

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Chaudhuri, L., Nicholson, A., Kalen, A. et al. Preferential selection of MnSOD transcripts in proliferating normal and cancer cells. Oncogene 31, 1207–1216 (2012). https://doi.org/10.1038/onc.2011.325

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