title: Regulation of alternative splicing of Bcl-x by IL-6, GM-CSF and TPA.
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 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.
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China.
authors.forename: Chang You
authors.initials: CY
authors.lastname: Li
authors.forename: Jia You
authors.initials: JY
authors.lastname: Chu
authors.forename: Jian Kun
authors.initials: JK
authors.lastname: Yu
authors.forename: Xiao Qin
authors.initials: XQ
authors.lastname: Huang
authors.forename: Xiao Juan
authors.initials: XJ
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Shi
authors.forename: Yan Chun
authors.initials: YC
authors.lastname: Che
authors.forename: Jiu Yong
authors.initials: JY
authors.lastname: Xie
mesh_terms: D017398:Alternative Splicing / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D005091:Exons; D017930:Genes, Reporter / Q000187:drug effects / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D007438:Introns; D020014:K562 Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism*; D012322:RNA Precursors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D051020:bcl-X Protein
chemical_list: C494811:BCL2L1 protein, human; D015850:Interleukin-6; D019253:Proto-Oncogene Proteins c-bcl-2; D012322:RNA Precursors; D012333:RNA, Messenger; D051020:bcl-X Protein; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013755:Tetradecanoylphorbol Acetate