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Splicing inhibition induces gene expression through canonical NF‐κB pathway and extracellular signal‐related kinase activation
Author(s) -
Khan Khalid,
Schneider-Poetsch Tilman,
Ishfaq Muhammad,
Ito Akihiro,
Yoshimoto Rei,
Mukaida Naofumi,
Yoshida Minoru
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.02.018
Subject(s) - rna splicing , promoter , alternative splicing , mapk/erk pathway , gene expression , microbiology and biotechnology , transcription (linguistics) , transcription factor , splicing factor , biology , regulation of gene expression , gene , signal transduction , kinase , chemistry , messenger rna , genetics , rna , linguistics , philosophy
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.