Inhibition of mRNA deadenylation and degradation by ultraviolet light.
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.
Gowrishankar
Gayatri
G
Institute of Biochemistry, Medical School Hannover, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany.
Winzen
Reinhard
R
Bollig
Frank
F
Ghebremedhin
Beniam
B
Redich
Natalie
N
Ritter
Birgit
B
Resch
Klaus
K
Kracht
Michael
M
Holtmann
Helmut
H
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
D016207:Cytokines; D016209:Interleukin-8; D012333:RNA, Messenger; D011061:Poly A; D000225:Adenine