Splicing inhibition induces gene expression through canonical NF-κB pathway and extracellular signal-related kinase activation

Khalid Khan, Tilman Schneider-Poetsch, Muhammad Ishfaq, Akihiro Ito, Rei Yoshimoto, Naofumi Mukaida, Minoru Yoshida

研究成果: Article

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Splicing, a process for mRNA maturation, is essential for correct gene expression after transcription. However, recent studies also suggest that splicing affects transcription, but its mechanism remains elusive. We previously reported that treatment with spliceostatin A (SSA), a specific splicing inhibitor targeting the splicing factor SF3b, leads to transcriptional activation of a small subset of genes. To investigate the underlying mechanism we utilized luciferase reporters driven by the Interleukin 8 (IL-8) and cytomegalovirus (CMV) promoters, as both recruit a similar set of transcription factors. We also found that SSA treatment led to increased extracellular signal-regulated protein kinase (ERK) activity and that chemical inhibition of ERK also led to decreased promoter activation. Systematic deletion studies suggested that NF-κB activation is mainly responsible for SSA-induced promoters activation.

元の言語English
ページ(範囲)1053-1057
ページ数5
ジャーナルFEBS Letters
588
発行部数6
DOI
出版物ステータスPublished - 18-03-2014

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All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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