Gle1 is a multifunctional DEAD-box protein regulator that modulates Ded1 in translation initiation

Timothy A Bolger, Susan R. Wente

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

DEAD-box protein (Dbp) family members are essential for gene expression; however, their precise roles and regulation are not fully defined. During messenger (m)RNA export, Gle1 bound to inositol hexakisphosphate (IP 6) acts via Dbp5 to facilitate remodeling of mRNA-protein complexes. In contrast, here we define a novel Gle1 role in translation initiation through regulation of a different DEAD-box protein, the initiation factor Ded1. We find that Gle1 physically and genetically interacts with Ded1. Surprisingly, whereas Gle1 stimulates Dbp5, it inhibits Ded1 ATPase activity in vitro, and IP 6 does not affect this inhibition. Functionally, a gle1-4 mutant specifically suppresses initiation defects in a ded1-120 mutant, and ded1 and gle1 mutants have complementary perturbations in AUG start site recognition. Consistent with this role in initiation, Gle1 inhibits translation in vitro in competent extracts. These results indicate that Gle1 has a direct role in initiation and negatively regulates Ded1. Together, the differential regulation of two distinct DEAD-box proteins by a common factor (Gle1) establishes a new paradigm for controlling gene expression and coupling translation with mRNA export.

Original languageEnglish (US)
Pages (from-to)39750-39759
Number of pages10
JournalJournal of Biological Chemistry
Volume286
Issue number46
DOIs
StatePublished - Nov 18 2011

Fingerprint

Gene expression
Proteins
Gene Expression
Peptide Initiation Factors
Messenger RNA
Phytic Acid
Essential Genes
Protein Biosynthesis
Adenosine Triphosphatases
RNA
Defects
In Vitro Techniques
Recognition (Psychology)
Inhibition (Psychology)

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Gle1 is a multifunctional DEAD-box protein regulator that modulates Ded1 in translation initiation. / Bolger, Timothy A; Wente, Susan R.

In: Journal of Biological Chemistry, Vol. 286, No. 46, 18.11.2011, p. 39750-39759.

Research output: Contribution to journalArticle

@article{57669b59442a4e1a9ecfbc36e8cb896c,
title = "Gle1 is a multifunctional DEAD-box protein regulator that modulates Ded1 in translation initiation",
abstract = "DEAD-box protein (Dbp) family members are essential for gene expression; however, their precise roles and regulation are not fully defined. During messenger (m)RNA export, Gle1 bound to inositol hexakisphosphate (IP 6) acts via Dbp5 to facilitate remodeling of mRNA-protein complexes. In contrast, here we define a novel Gle1 role in translation initiation through regulation of a different DEAD-box protein, the initiation factor Ded1. We find that Gle1 physically and genetically interacts with Ded1. Surprisingly, whereas Gle1 stimulates Dbp5, it inhibits Ded1 ATPase activity in vitro, and IP 6 does not affect this inhibition. Functionally, a gle1-4 mutant specifically suppresses initiation defects in a ded1-120 mutant, and ded1 and gle1 mutants have complementary perturbations in AUG start site recognition. Consistent with this role in initiation, Gle1 inhibits translation in vitro in competent extracts. These results indicate that Gle1 has a direct role in initiation and negatively regulates Ded1. Together, the differential regulation of two distinct DEAD-box proteins by a common factor (Gle1) establishes a new paradigm for controlling gene expression and coupling translation with mRNA export.",
author = "Bolger, {Timothy A} and Wente, {Susan R.}",
year = "2011",
month = "11",
day = "18",
doi = "10.1074/jbc.M111.299321",
language = "English (US)",
volume = "286",
pages = "39750--39759",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "46",

}

TY - JOUR

T1 - Gle1 is a multifunctional DEAD-box protein regulator that modulates Ded1 in translation initiation

AU - Bolger, Timothy A

AU - Wente, Susan R.

PY - 2011/11/18

Y1 - 2011/11/18

N2 - DEAD-box protein (Dbp) family members are essential for gene expression; however, their precise roles and regulation are not fully defined. During messenger (m)RNA export, Gle1 bound to inositol hexakisphosphate (IP 6) acts via Dbp5 to facilitate remodeling of mRNA-protein complexes. In contrast, here we define a novel Gle1 role in translation initiation through regulation of a different DEAD-box protein, the initiation factor Ded1. We find that Gle1 physically and genetically interacts with Ded1. Surprisingly, whereas Gle1 stimulates Dbp5, it inhibits Ded1 ATPase activity in vitro, and IP 6 does not affect this inhibition. Functionally, a gle1-4 mutant specifically suppresses initiation defects in a ded1-120 mutant, and ded1 and gle1 mutants have complementary perturbations in AUG start site recognition. Consistent with this role in initiation, Gle1 inhibits translation in vitro in competent extracts. These results indicate that Gle1 has a direct role in initiation and negatively regulates Ded1. Together, the differential regulation of two distinct DEAD-box proteins by a common factor (Gle1) establishes a new paradigm for controlling gene expression and coupling translation with mRNA export.

AB - DEAD-box protein (Dbp) family members are essential for gene expression; however, their precise roles and regulation are not fully defined. During messenger (m)RNA export, Gle1 bound to inositol hexakisphosphate (IP 6) acts via Dbp5 to facilitate remodeling of mRNA-protein complexes. In contrast, here we define a novel Gle1 role in translation initiation through regulation of a different DEAD-box protein, the initiation factor Ded1. We find that Gle1 physically and genetically interacts with Ded1. Surprisingly, whereas Gle1 stimulates Dbp5, it inhibits Ded1 ATPase activity in vitro, and IP 6 does not affect this inhibition. Functionally, a gle1-4 mutant specifically suppresses initiation defects in a ded1-120 mutant, and ded1 and gle1 mutants have complementary perturbations in AUG start site recognition. Consistent with this role in initiation, Gle1 inhibits translation in vitro in competent extracts. These results indicate that Gle1 has a direct role in initiation and negatively regulates Ded1. Together, the differential regulation of two distinct DEAD-box proteins by a common factor (Gle1) establishes a new paradigm for controlling gene expression and coupling translation with mRNA export.

UR - http://www.scopus.com/inward/record.url?scp=81155154337&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=81155154337&partnerID=8YFLogxK

U2 - 10.1074/jbc.M111.299321

DO - 10.1074/jbc.M111.299321

M3 - Article

VL - 286

SP - 39750

EP - 39759

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 46

ER -