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

Fingerprint

Gene expression
Signal Transduction
Phosphotransferases
Chemical activation
Gene Expression
Transcription
Essential Genes
Extracellular Signal-Regulated MAP Kinases
Luciferases
Cytomegalovirus
Interleukin-8
Protein Kinases
Transcriptional Activation
Transcription Factors
Messenger RNA
Genes
spliceostatin A

All Science Journal Classification (ASJC) codes

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

Cite this

Khan, Khalid ; Schneider-Poetsch, Tilman ; Ishfaq, Muhammad ; Ito, Akihiro ; Yoshimoto, Rei ; Mukaida, Naofumi ; Yoshida, Minoru. / Splicing inhibition induces gene expression through canonical NF-κB pathway and extracellular signal-related kinase activation. In: FEBS Letters. 2014 ; Vol. 588, No. 6. pp. 1053-1057.
@article{ce774622a0eb464aa1b82346fb882dab,
title = "Splicing inhibition induces gene expression through canonical NF-κB pathway and extracellular signal-related kinase activation",
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.",
author = "Khalid Khan and Tilman Schneider-Poetsch and Muhammad Ishfaq and Akihiro Ito and Rei Yoshimoto and Naofumi Mukaida and Minoru Yoshida",
year = "2014",
month = "3",
day = "18",
doi = "10.1016/j.febslet.2014.02.018",
language = "English",
volume = "588",
pages = "1053--1057",
journal = "FEBS Letters",
issn = "0014-5793",
publisher = "Elsevier",
number = "6",

}

Splicing inhibition induces gene expression through canonical NF-κB pathway and extracellular signal-related kinase activation. / Khan, Khalid; Schneider-Poetsch, Tilman; Ishfaq, Muhammad; Ito, Akihiro; Yoshimoto, Rei; Mukaida, Naofumi; Yoshida, Minoru.

In: FEBS Letters, Vol. 588, No. 6, 18.03.2014, p. 1053-1057.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Splicing inhibition induces gene expression through canonical NF-κB pathway and extracellular signal-related kinase activation

AU - Khan, Khalid

AU - Schneider-Poetsch, Tilman

AU - Ishfaq, Muhammad

AU - Ito, Akihiro

AU - Yoshimoto, Rei

AU - Mukaida, Naofumi

AU - Yoshida, Minoru

PY - 2014/3/18

Y1 - 2014/3/18

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84896068608&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84896068608&partnerID=8YFLogxK

U2 - 10.1016/j.febslet.2014.02.018

DO - 10.1016/j.febslet.2014.02.018

M3 - Article

C2 - 24561197

AN - SCOPUS:84896068608

VL - 588

SP - 1053

EP - 1057

JO - FEBS Letters

JF - FEBS Letters

SN - 0014-5793

IS - 6

ER -