PMID- 8668145 OWN - NLM STAT- MEDLINE DCOM- 19960808 LR - 20210526 IS - 0270-7306 (Print) IS - 1098-5549 (Electronic) IS - 0270-7306 (Linking) VI - 16 IP - 7 DP - 1996 Jul TI - Interleukin-11 mRNA stabilization in phorbol ester-stimulated primate bone marrow stromal cells. PG - 3300-7 AB - 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 (5'UTR) and coding region of the IL-11 mRNA but has lost the poly(A) tail and the 3'UTR. 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 3'UTR 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 5'UTR, coding region, and 3'UTR 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. FAU - Yang, L AU - Yang L AD - Department of Biochemistry and Molecular Biology, Walter Oncology Center, Indiana University School of Medicine, Indianapolis, 46202, USA. FAU - Steussy, C N AU - Steussy CN FAU - Fuhrer, D K AU - Fuhrer DK FAU - Hamilton, J AU - Hamilton J FAU - Yang, Y C AU - Yang YC LA - eng GR - R01DK43105/DK/NIDDK NIH HHS/United States GR - R01HL48819/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Mol Cell Biol JT - Molecular and cellular biology JID - 8109087 RN - 0 (DNA Probes) RN - 0 (Enzyme Inhibitors) RN - 0 (Interleukin-11) RN - 0 (Isoflavones) RN - 0 (Isoquinolines) RN - 0 (Naphthalenes) RN - 0 (Piperazines) RN - 0 (RNA, Messenger) RN - 0 (Recombinant Fusion Proteins) RN - 1CC1JFE158 (Dactinomycin) RN - 84477-87-2 (1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine) RN - DH2M523P0H (Genistein) RN - EC 1.13.12.- (Luciferases) RN - EC 2.7.11.13 (Protein Kinase C) RN - I271P23G24 (calphostin C) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) SB - IM MH - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine MH - Animals MH - *Bone Marrow Cells MH - Cell Line MH - Cell Nucleus/metabolism MH - DNA Probes MH - Dactinomycin/pharmacology MH - Enzyme Inhibitors/pharmacology MH - *Gene Expression Regulation/drug effects MH - Genistein MH - Interleukin-11/*biosynthesis MH - Isoflavones/pharmacology MH - Isoquinolines/pharmacology MH - Kinetics MH - Luciferases/biosynthesis MH - Naphthalenes/pharmacology MH - Open Reading Frames MH - Piperazines/pharmacology MH - Primates MH - Protein Kinase C/antagonists & inhibitors MH - *RNA Processing, Post-Transcriptional MH - RNA, Messenger/*metabolism MH - Recombinant Fusion Proteins/biosynthesis MH - Stromal Cells/immunology MH - Tetradecanoylphorbol Acetate/*pharmacology MH - Time Factors MH - Transcription, Genetic MH - Transfection PMC - PMC231324 EDAT- 1996/07/01 00:00 MHDA- 1996/07/01 00:01 PMCR- 1996/07/01 CRDT- 1996/07/01 00:00 PHST- 1996/07/01 00:00 [pubmed] PHST- 1996/07/01 00:01 [medline] PHST- 1996/07/01 00:00 [entrez] PHST- 1996/07/01 00:00 [pmc-release] AID - 10.1128/MCB.16.7.3300 [doi] PST - ppublish SO - Mol Cell Biol. 1996 Jul;16(7):3300-7. doi: 10.1128/MCB.16.7.3300.