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

Authors
  • Khan, Khalid
  • Schneider-Poetsch, Tilman
  • Ishfaq, Muhammad
  • Ito, Akihiro
  • Yoshimoto, Rei
  • Mukaida, Naofumi
  • Yoshida, Minoru1, 2, 3, 4, 5, 6, 7
  • 1 Chemical Genetic Laboratory
  • 2 RIKEN
  • 3 Chemical Genomics Research Group
  • 4 RIKEN Center for Sustainable Resource Science
  • 5 Graduate School of Science and Engineering
  • 6 Saitama University
  • 7 Cancer Research Institute of Kanazawa University
Type
Published Article
Journal
FEBS Letters
Publisher
Wiley (John Wiley & Sons)
Publication Date
Jan 01, 2014
Accepted Date
Feb 05, 2014
Volume
588
Issue
6
Pages
1053–1057
Identifiers
DOI: 10.1016/j.febslet.2014.02.018
Source
Elsevier
Keywords
License
Unknown

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.

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