Evidence for general stabilization of mRNAs in response to UV light.
mRNA stabilization plays an important role in the changes in protein expression initiated by inducers of inflammation or direct cell stress such as UV light. This study provides evidence that stabilization in response to UV light differs from that induced by proinflammatory stimuli such as bacterial lipopolysaccharide or interleukin (IL)-1. Firstly, UV-induced stabilization is independent of the p38 MAP kinase pathway, which has previously been shown to mediate stabilization induced by IL-1 or lipopolysaccharide. UV-induced mRNA stabilization was insensitive to the dominant negative forms of p38 MAP kinase and its substrate MAP kinase-activated protein kinase 2 (MK2), or to the p38 MAP kinase inhibitor SB 203580, demonstrating that it occurs through a different signaling mechanism. Secondly, UV-induced stabilization exhibits a different transcript selectivity. Activation of the p38 MAP kinase pathway, by expressing active MAP kinase kinase 6, induced stabilization only of transcripts containing AU-rich elements. UV light also induced stabilization of transcripts lacking AU-rich elements. This effect could not be mimicked by expressing MEKK1, an upstream activator of the p38, JNK, ERK and NF-kappaB pathways. UV light also stabilized endogenous histone mRNA, which lacks AU-rich elements and a poly(A) tail. This effect was not mimicked by active MAP kinase kinase 6 and not sensitive to a p38 MAP kinase inhibitor. This suggests that UV light induces stabilization through a mechanism that is independent of p38 MAP kinase and affects a broad spectrum of mRNAs.
Bollig
Frank
F
Institute of Pharmacology, Medical School Hannover, Germany.
Winzen
Reinhard
R
Kracht
Michael
M
Ghebremedhin
Beniam
B
Ritter
Birgit
B
Wilhelm
Arno
A
Resch
Klaus
K
Holtmann
Helmut
H
D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D024202:Electrophoretic Mobility Shift Assay; D004789:Enzyme Activation; D006367:HeLa Cells; D006657:Histones / Q000235:genetics; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects*; D016601:RNA-Binding Proteins / Q000378:metabolism; D014158:Transcription, Genetic; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases
D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D006657:Histones; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases