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PMID: 10523622 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Eukaryotic translation initiation factor 4AIII (eIF4AIII) is functionally distinct from eIF4AI and eIF4AII.

Molecular and cellular biology ·Vol. 19 ·No. 11 ·1999-11-00 ·Pages 7336-46

Li Q, Imataka H, Morino S, Rogers GW, Richter-Cook NJ, Merrick WC, Sonenberg N

Abstract

Eukaryotic initiation factor 4A (eIF4A) is an RNA-dependent ATPase and ATP-dependent RNA helicase that is thought to melt the 5' proximal secondary structure of eukaryotic mRNAs to facilitate attachment of the 40S ribosomal subunit. eIF4A functions in a complex termed eIF4F with two other initiation factors (eIF4E and eIF4G). Two isoforms of eIF4A, eIF4AI and eIF4AII, which are encoded by two different genes, are functionally indistinguishable. A third member of the eIF4A family, eIF4AIII, whose human homolog exhibits 65% amino acid identity to human eIF4AI, has also been cloned from Xenopus and tobacco, but its function in translation has not been characterized. In this study, human eIF4AIII was characterized biochemically. While eIF4AIII, like eIF4AI, exhibits RNA-dependent ATPase activity and ATP-dependent RNA helicase activity, it fails to substitute for eIF4AI in an in vitro-reconstituted 40S ribosome binding assay. Instead, eIF4AIII inhibits translation in a reticulocyte lysate system. In addition, whereas eIF4AI binds independently to the middle and carboxy-terminal fragments of eIF4G, eIF4AIII binds to the middle fragment only. These functional differences between eIF4AI and eIF4AIII suggest that eIF4AIII might play an inhibitory role in translation under physiological conditions.

MeSH Terms
Adenosine Triphosphatases/metabolism Amino Acid Sequence Conserved Sequence DNA Helicases/metabolism Eukaryotic Cells Eukaryotic Initiation Factor-4A Eukaryotic Initiation Factor-4G Gene Expression Gene Library Models, Theoretical Molecular Sequence Data Multigene Family Peptide Initiation Factors/genetics,metabolism Protein Binding Protein Biosynthesis Protein Isoforms Ribosomes/metabolism Sequence Analysis, DNA Sequence Homology, Amino Acid
Chemicals
Eukaryotic Initiation Factor-4G Peptide Initiation Factors Protein Isoforms Eukaryotic Initiation Factor-4A Adenosine Triphosphatases RNA-dependent ATPase DNA Helicases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Li Q
Department of Biochemistry, McGill Cancer Center, McGill University, Montreal, Quebec, Canada H3G 1Y6.
Imataka H
Morino S
Rogers G W
Richter-Cook N J
Merrick W C
Sonenberg N
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
Published
1999-11-00
Pages
7336-46
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC84727
Subset
IM
Databases
GENBANK
P38919
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