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- Title
Inhibition of mRNA deadenylation and degradation by ultraviolet light.
- Authors
Gowrishankar, Gayatri; Winzen, Reinhard; Bollig, Frank; Ghebremedhin, Beniam; Redich, Natalie; Ritter, Birgit; Resch, Klaus; Kracht, Michael; Holtmann, Helmut
- Abstract
Post-transcriptional mechanisms contribute to the changes in gene expression induced by cell stress. The effect of UV-B light on mRNA degradation in HeLa cells was investigated using a transcriptional chase system to determine the decay kinetics of tet-off vector-derived mRNAs containing or lacking a destabilizing AU-rich element. Degradation of both mRNAs was strongly inhibited in cells exposed to UV-B light. Removal of the poly(A)-tail, considered a crucial step in mRNA degradation, was strikingly impaired. UV light also inhibited deadenylation and degradation of endogenous mRNA of the chemoattractant cytokine interleukin (IL)-8. Both effects occurred rapidly and independently of newly induced genes. Importantly, stabilization of IL-8 mRNA was accompanied by a strong increase in the duration of IL-8 protein formation. Furthermore, general inhibition of protein synthesis, a hallmark of the response to cell stress, required far higher doses of UV-B than inhibition of mRNA deadenylation and degradation. The difference in sensitivity of cells to these effects of UV-B light establishes a dose range in which mRNA stabilization can lead to dramatically enhanced expression of proteins derived from normally unstable mRNAs, such as those of inflammatory cytokines, growth factors and proto-oncogenes, and thereby have a major impact on the response to UV light.
- Subjects
GENE expression; CELLS; ULTRAVIOLET radiation; MESSENGER RNA; HELA cells
- Publication
Biological Chemistry, 2005, Vol 386, Issue 12, p1287
- ISSN
1431-6730
- Publication type
Article
- DOI
10.1515/BC.2005.146