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PMID: 16287867 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Eukaryotic translation initiation factor 4E availability controls the switch between cap-dependent and internal ribosomal entry site-mediated translation.

Molecular and cellular biology ·Vol. 25 ·No. 23 ·2005-12-00 ·Pages 10556-65

Svitkin YV, Herdy B, Costa-Mattioli M, Gingras AC, Raught B, Sonenberg N

Abstract

Translation of m7G-capped cellular mRNAs is initiated by recruitment of ribosomes to the 5' end of mRNAs via eukaryotic translation initiation factor 4F (eIF4F), a heterotrimeric complex comprised of a cap-binding subunit (eIF4E) and an RNA helicase (eIF4A) bridged by a scaffolding molecule (eIF4G). Internal translation initiation bypasses the requirement for the cap and eIF4E and occurs on viral and cellular mRNAs containing internal ribosomal entry sites (IRESs). Here we demonstrate that eIF4E availability plays a critical role in the switch from cap-dependent to IRES-mediated translation in picornavirus-infected cells. When both capped and IRES-containing mRNAs are present (as in intact cells or in vitro translation extracts), a decrease in the amount of eIF4E associated with the eIF4F complex elicits a striking increase in IRES-mediated viral mRNA translation. This effect is not observed in translation extracts depleted of capped mRNAs, indicating that capped mRNAs compete with IRES-containing mRNAs for translation. These data explain numerous reported observations where viral mRNAs are preferentially translated during infection.

MeSH Terms
Animals Cell Line Cell-Free System Encephalomyocarditis virus/genetics Eukaryotic Initiation Factor-4F/genetics,metabolism Gene Expression Regulation Humans Mice Protein Binding Protein Biosynthesis Protein Transport RNA Caps/genetics,metabolism RNA, Messenger/genetics,metabolism RNA, Small Interfering/genetics,metabolism RNA, Viral/genetics,metabolism Ribosomes/genetics,metabolism Virus Replication
Chemicals
Eukaryotic Initiation Factor-4F RNA Caps RNA, Messenger RNA, Small Interfering RNA, Viral
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Svitkin Yuri V
Department of Biochemistry, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec, Canada H3G 1Y6.
Herdy Barbara
Costa-Mattioli Mauro
Gingras Anne-Claude
Raught Brian
Sonenberg Nahum
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.25.23.10556-10565.2005
Published
2005-12-00
Pages
10556-65
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1291233
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.25.23.10556-10565.2005 PMC Full Text View journal details
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