Regulation of alternative splicing of Bcl-x by IL-6, GM-CSF and TPA
| Autor: | Jiuyong Xie, Chang-you Li, Yan Chun Che, Huang Xq, Li Shi, Xiao Juan Liu, Jia You Chu, Jian Kun Yu |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
bcl-X Protein
Biology Exon Genes Reporter Cell Line Tumor RNA Precursors Humans RNA Messenger Molecular Biology Gene Messenger RNA Interleukin-6 Alternative splicing Intron Granulocyte-Macrophage Colony-Stimulating Factor RNA Exons Cell Biology Molecular biology Introns Alternative Splicing Proto-Oncogene Proteins c-bcl-2 RNA splicing Tetradecanoylphorbol Acetate K562 Cells K562 cells |
| Zdroj: | Cell Research. 14:473-479 |
| ISSN: | 1748-7838 1001-0602 |
| Popis: | The splicing of many alternative exons in the precursor messenger RNA (pre-mRNA) is regulated by extracellular factors but the underlying molecular bases remain unclear. Here we report the differential regulation of Bcl-x pre-mRNA splicing by extracellular factors and their distinct requirements for pre-mRNA elements. In K562 leukemia cells, treatment with interleukin-6 (IL-6) or granulocyte-macrophage colony stimulating factor (GM-CSF) reduced the proportion of the Bcl-xL variant mRNA while treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) had no effect. In U251 glioma cells, however, TPA efficiently increased the Bcl-xL level. These regulations were also seen for a transfected splicing reporter mini-gene. Further analyses of deletion mutants indicate that nucleotides 1-176 on the downstream intron are required for the IL-6 effect, whereas additional nucleotides 177-284 are essential for the GM-CSF effects. As for the TPA effect, only nucleotides 1-76 are required in the downstream intron, Thus UK-6, GM-CSF and TPA differentially regulate Bcl-x splicing and require specific intronic pre-mRNA sequences for their respective effects. |
| Databáze: | OpenAIRE |
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