Inhibition of ribosome recruitment induces stress granule formation independently of eukaryotic initiation factor 2alpha phosphorylation

Rachid Mazroui; Rami Sukarieh; Marie-Eve Bordeleau; Randal J Kaufman; Peter Northcote; Junichi Tanaka; Imed Gallouzi; Jerry Pelletier

doi:10.1091/mbc.e06-04-0318

Inhibition of ribosome recruitment induces stress granule formation independently of eukaryotic initiation factor 2alpha phosphorylation

Mol Biol Cell. 2006 Oct;17(10):4212-9. doi: 10.1091/mbc.e06-04-0318. Epub 2006 Jul 26.

Authors

Rachid Mazroui¹, Rami Sukarieh, Marie-Eve Bordeleau, Randal J Kaufman, Peter Northcote, Junichi Tanaka, Imed Gallouzi, Jerry Pelletier

Affiliation

¹ Department of Biochemistry, McGill University, Montreal, Quebec, Canada H3G 1Y6.

Abstract

Cytoplasmic aggregates known as stress granules (SGs) arise as a consequence of cellular stress and contain stalled translation preinitiation complexes. These foci are thought to serve as sites of mRNA storage or triage during the cell stress response. SG formation has been shown to require induction of eukaryotic initiation factor (eIF)2alpha phosphorylation. Herein, we investigate the potential role of other initiation factors in this process and demonstrate that interfering with eIF4A activity, an RNA helicase required for the ribosome recruitment phase of translation initiation, induces SG formation and that this event is not dependent on eIF2alpha phosphorylation. We also show that inhibition of eIF4A activity does not impair the ability of eIF2alpha to be phosphorylated under stress conditions. Furthermore, we observed SG assembly upon inhibition of cap-dependent translation after poliovirus infection. We propose that SG modeling can occur via both eIF2alpha phosphorylation-dependent and -independent pathways that target translation initiation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antigens, Surface / metabolism
Carrier Proteins / metabolism
Cytoplasmic Granules / metabolism*
DNA Helicases
ELAV Proteins
ELAV-Like Protein 1
Eukaryotic Initiation Factor-2 / metabolism*
Eukaryotic Initiation Factor-2 / physiology
Eukaryotic Initiation Factor-4A / genetics
Eukaryotic Initiation Factor-4A / metabolism*
Eukaryotic Initiation Factor-4A / physiology*
HeLa Cells
Humans
Models, Genetic
Peptide Initiation Factors / metabolism*
Phosphorylation
Poliovirus / genetics
Poly-ADP-Ribose Binding Proteins
Protein Biosynthesis
RNA Helicases
RNA Recognition Motif Proteins
RNA, Small Interfering
RNA-Binding Proteins / metabolism
Ribosomes / metabolism*

Substances

Antigens, Surface
Carrier Proteins
ELAV Proteins
ELAV-Like Protein 1
ELAVL1 protein, human
Eukaryotic Initiation Factor-2
Peptide Initiation Factors
Poly-ADP-Ribose Binding Proteins
RNA Recognition Motif Proteins
RNA, Small Interfering
RNA-Binding Proteins
Eukaryotic Initiation Factor-4A
DNA Helicases
G3BP1 protein, human
RNA Helicases