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Interleukin-11 mRNA Stabilization in Phorbol Ester-Stimulated Primate Bone Marrow Stromal Cells

1996; Taylor & Francis; Volume: 16; Issue: 7 Linguagem: Inglês

10.1128/mcb.16.7.3300

1098-5549

Liu Yang, C.N. Steussy, D Führer, Jean Hamilton, Yu‐Chung Yang,

Cytokine Signaling Pathways and Interactions

12-O-Tetradecanoylphorbol-13-acetate (TPA) stimulation of PU-34 cells, a primate bone marrow stromal cell line, resulted in a prolonged elevation of interleukin-11 (IL-11) mRNA, which can be inhibited by protein synthesis inhibitors.Nuclear run-on assays and actinomycin D experiments demonstrated that the up-regulation of IL-11 gene expression is mainly controlled at the posttranscriptional level through the protein kinase C (PKC) pathway.Inhibition of PKC activity by calphostin C generated an IL-11 mRNA degradation intermediate in TPA-stimulated PU-34 cells.This intermediate retains the 5 untranslated region (5UTR) and coding region of the IL-11 mRNA but has lost the poly(A) tail and the 3UTR.The mechanisms underlying IL-11 mRNA stabilization were further investigated by transfections with a variety of chimeric IL-11 constructs and deletion mutants.Two important observations were made from these transient expression experiments: (i) the same 3UTR of IL-11 mRNA shown to confer instability in one chimeric transcript may not function as a destabilizer in another chimeric RNA, and (ii) the 5UTR, coding region, and 3UTR all contribute to IL-11 mRNA decay, and labile IL-11 deletion transcripts are not necessarily stabilized by TPA stimulation.Our study suggests that multiple regions within the IL-11 mRNA are involved in TPA-stimulated IL-11 mRNA stabilization, possibly through a unique RNA folding conformation involving interactions of various RNA sequences within the IL-11 mRNA molecule.