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

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1053-1057
Number of pages5
JournalFEBS Letters
Volume588
Issue number6
DOIs
Publication statusPublished - 18-03-2014

All Science Journal Classification (ASJC) codes

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

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    Khan, K., Schneider-Poetsch, T., Ishfaq, M., Ito, A., Yoshimoto, R., Mukaida, N., & Yoshida, M. (2014). Splicing inhibition induces gene expression through canonical NF-κB pathway and extracellular signal-related kinase activation. FEBS Letters, 588(6), 1053-1057. https://doi.org/10.1016/j.febslet.2014.02.018