title: 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.
authors.affiliation: Institute of Biochemistry, Medical School Hannover, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany.
authors.forename: Gayatri
authors.initials: G
authors.lastname: Gowrishankar
authors.forename: Reinhard
authors.initials: R
authors.lastname: Winzen
authors.forename: Frank
authors.initials: F
authors.lastname: Bollig
authors.forename: Beniam
authors.initials: B
authors.lastname: Ghebremedhin
authors.forename: Natalie
authors.initials: N
authors.lastname: Redich
authors.forename: Birgit
authors.initials: B
authors.lastname: Ritter
authors.forename: Klaus
authors.initials: K
authors.lastname: Resch
authors.forename: Michael
authors.initials: M
authors.lastname: Kracht
authors.forename: Helmut
authors.initials: H
authors.lastname: Holtmann
mesh_terms: D000225:Adenine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006367:HeLa Cells / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D011061:Poly A / Q000235:genetics / Q000378:metabolism; D020871:RNA Stability / Q000235:genetics / Q000502:physiology / Q000528:radiation effects*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000528:radiation effects*; D014466:Ultraviolet Rays
chemical_list: D016207:Cytokines; D016209:Interleukin-8; D012333:RNA, Messenger; D011061:Poly A; D000225:Adenine