Preferential selection of MnSOD transcripts in proliferating normal and cancer cells.

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.

journal_name

Oncogene

journal_title

Oncogene

authors

Chaudhuri L,Nicholson AM,Kalen AL,Goswami PC

doi

10.1038/onc.2011.325

subject

Has Abstract

pub_date

2012-03-08 00:00:00

pages

1207-16

issue

10

eissn

0950-9232

issn

1476-5594

pii

onc2011325

journal_volume

31

pub_type

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