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Vol. 14, No. 10, pp. 1236-1248, May 15, 2000
1 Department of Pharmacology, University of California San
Diego, La Jolla, California 92093 USA; 2 Protein Interaction
Laboratory, University of Southern Denmark-Odense, DK-5230 Odense M,
Denmark; 3 Department of Neuroscience, University of
California San Diego, La Jolla, California 92093 USA;
4 Department of Medical Genetics, Max-Delbruck Center for
Molecular Medicine, 13122 Berlin, Germany
Regulated mRNA turnover is a highly important process, but its
mechanism is poorly understood. Using interleukin-2 (IL-2) mRNA as a
model, we described a role for the JNK-signaling pathway in
stabilization of IL-2 mRNA during T-cell activation, acting via a JNK
response element (JRE) in the 5' untranslated region (UTR). We have
now identified two major RNA-binding proteins, nucleolin and YB-1, that
specifically bind to the JRE. Binding of both proteins is required for
IL-2 mRNA stabilization induced by T-cell activation signals and for
JNK-induced stabilization in a cell-free system that duplicates
essential features of regulated mRNA decay. Nucleolin and YB-1 are
required for formation of an IL-2 mRNP complex that responds to
specific mRNA stabilizing signals.
[Key Words: Nucleolin; JNK; T-cell activation; stabilization; trans-acting factors]
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