Inhibition of mRNA deadenylation and degradation by ultraviolet light.

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.

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@article{Gowrishankar2005InhibitionOM, title={Inhibition of mRNA deadenylation and degradation by ultraviolet light.}, author={Gayatri Gowrishankar and Reinhard Winzen and Frank Bollig and Beniam Ghebremedhin and Natalie Redich and Birgit Ritter and Klaus Resch and Michael Kracht and Helmut Holtmann}, journal={Biological chemistry}, year={2005}, volume={386 12}, pages={1287-93} }