Hydrogen peroxide induces stress granule formation independent of eIF2α phosphorylation

Mohamed Emara, Ken Fujimura, Daniele Sciaranghella, Victoria Ivanova, Pavel Ivanov, Paul Anderson

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

In cells exposed to environmental stress, inhibition of translation initiation conserves energy for the repair of cellular damage. Untranslated mRNAs that accumulate in these cells move to discrete cytoplasmic foci known as stress granules (SGs). The assembly of SGs helps cells to survive under adverse environmental conditions. We have analyzed the mechanism by which hydrogen peroxide (H 2O 2)-induced oxidative stress inhibits translation initiation and induces SG assembly in mammalian cells. Our data indicate that H 2O 2 inhibits translation and induces the assembly of SGs. The assembly of H 2O 2-induced SGs is independent of the phosphorylation of eIF2α, a major trigger of SG assembly, but requires remodeling of the cap-binding eIF4F complex. Moreover, H 2O 2-induced SGs are compositionally distinct from canonical SGs, and targeted knockdown of eIF4E, a protein required for canonical translation initiation, inhibits H 2O 2-induced SG assembly. Our data reveal new aspects of translational regulation induced by oxidative insults.

Original languageEnglish
Pages (from-to)763-769
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume423
Issue number4
DOIs
Publication statusPublished - 13 Jul 2012

Fingerprint

Phosphorylation
Hydrogen Peroxide
Oxidative Stress
Messenger RNA
Oxidative stress
Proteins
Repair
Cells

Keywords

  • EIF2
  • EIF4E
  • Oxidative stress
  • RNA
  • Stress granules
  • Translation

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Hydrogen peroxide induces stress granule formation independent of eIF2α phosphorylation. / Emara, Mohamed; Fujimura, Ken; Sciaranghella, Daniele; Ivanova, Victoria; Ivanov, Pavel; Anderson, Paul.

In: Biochemical and Biophysical Research Communications, Vol. 423, No. 4, 13.07.2012, p. 763-769.

Research output: Contribution to journalArticle

Emara, Mohamed ; Fujimura, Ken ; Sciaranghella, Daniele ; Ivanova, Victoria ; Ivanov, Pavel ; Anderson, Paul. / Hydrogen peroxide induces stress granule formation independent of eIF2α phosphorylation. In: Biochemical and Biophysical Research Communications. 2012 ; Vol. 423, No. 4. pp. 763-769.
@article{8cd4ff67ebdf4d358a82231da8b4f42e,
title = "Hydrogen peroxide induces stress granule formation independent of eIF2α phosphorylation",
abstract = "In cells exposed to environmental stress, inhibition of translation initiation conserves energy for the repair of cellular damage. Untranslated mRNAs that accumulate in these cells move to discrete cytoplasmic foci known as stress granules (SGs). The assembly of SGs helps cells to survive under adverse environmental conditions. We have analyzed the mechanism by which hydrogen peroxide (H 2O 2)-induced oxidative stress inhibits translation initiation and induces SG assembly in mammalian cells. Our data indicate that H 2O 2 inhibits translation and induces the assembly of SGs. The assembly of H 2O 2-induced SGs is independent of the phosphorylation of eIF2α, a major trigger of SG assembly, but requires remodeling of the cap-binding eIF4F complex. Moreover, H 2O 2-induced SGs are compositionally distinct from canonical SGs, and targeted knockdown of eIF4E, a protein required for canonical translation initiation, inhibits H 2O 2-induced SG assembly. Our data reveal new aspects of translational regulation induced by oxidative insults.",
keywords = "EIF2, EIF4E, Oxidative stress, RNA, Stress granules, Translation",
author = "Mohamed Emara and Ken Fujimura and Daniele Sciaranghella and Victoria Ivanova and Pavel Ivanov and Paul Anderson",
year = "2012",
month = "7",
day = "13",
doi = "10.1016/j.bbrc.2012.06.033",
language = "English",
volume = "423",
pages = "763--769",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "4",

}

TY - JOUR

T1 - Hydrogen peroxide induces stress granule formation independent of eIF2α phosphorylation

AU - Emara, Mohamed

AU - Fujimura, Ken

AU - Sciaranghella, Daniele

AU - Ivanova, Victoria

AU - Ivanov, Pavel

AU - Anderson, Paul

PY - 2012/7/13

Y1 - 2012/7/13

N2 - In cells exposed to environmental stress, inhibition of translation initiation conserves energy for the repair of cellular damage. Untranslated mRNAs that accumulate in these cells move to discrete cytoplasmic foci known as stress granules (SGs). The assembly of SGs helps cells to survive under adverse environmental conditions. We have analyzed the mechanism by which hydrogen peroxide (H 2O 2)-induced oxidative stress inhibits translation initiation and induces SG assembly in mammalian cells. Our data indicate that H 2O 2 inhibits translation and induces the assembly of SGs. The assembly of H 2O 2-induced SGs is independent of the phosphorylation of eIF2α, a major trigger of SG assembly, but requires remodeling of the cap-binding eIF4F complex. Moreover, H 2O 2-induced SGs are compositionally distinct from canonical SGs, and targeted knockdown of eIF4E, a protein required for canonical translation initiation, inhibits H 2O 2-induced SG assembly. Our data reveal new aspects of translational regulation induced by oxidative insults.

AB - In cells exposed to environmental stress, inhibition of translation initiation conserves energy for the repair of cellular damage. Untranslated mRNAs that accumulate in these cells move to discrete cytoplasmic foci known as stress granules (SGs). The assembly of SGs helps cells to survive under adverse environmental conditions. We have analyzed the mechanism by which hydrogen peroxide (H 2O 2)-induced oxidative stress inhibits translation initiation and induces SG assembly in mammalian cells. Our data indicate that H 2O 2 inhibits translation and induces the assembly of SGs. The assembly of H 2O 2-induced SGs is independent of the phosphorylation of eIF2α, a major trigger of SG assembly, but requires remodeling of the cap-binding eIF4F complex. Moreover, H 2O 2-induced SGs are compositionally distinct from canonical SGs, and targeted knockdown of eIF4E, a protein required for canonical translation initiation, inhibits H 2O 2-induced SG assembly. Our data reveal new aspects of translational regulation induced by oxidative insults.

KW - EIF2

KW - EIF4E

KW - Oxidative stress

KW - RNA

KW - Stress granules

KW - Translation

UR - http://www.scopus.com/inward/record.url?scp=84863827090&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863827090&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2012.06.033

DO - 10.1016/j.bbrc.2012.06.033

M3 - Article

VL - 423

SP - 763

EP - 769

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 4

ER -