ABSTRACT
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 of the downstream intron are required for the IL-6 effect, whereas additional nucleotides 177-284 are essential for the GM-CSF effect. As for the TPA effect, only nucleotides 1-76 are required in the downstream intron. Thus, IL-6, GM-CSF and TPA differentially regulate Bcl-x splicing and require specific intronic pre-mRNA sequences for their respective effects.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (No. 39993420) to Chu JY, and by the University of Manitoba to Xie JY.
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LI, C., CHU, J., YU, J. et al. Regulation of alternative splicing of Bcl-x by IL-6, GM-CSF and TPA. Cell Res 14, 473–479 (2004). https://doi.org/10.1038/sj.cr.7290250
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DOI: https://doi.org/10.1038/sj.cr.7290250
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