eIF4AIII enhances translation of nuclear cap-binding complex-bound mRNAs by promoting disruption of secondary structures in 5'UTR

Junho Choe, Incheol Ryu, Ok H yun Park, Joori Park, Hana Cho, Jin S eon Yoo, Sung W ook Chi, Min K yung Kim, Hyun K yu Song, Yoon K i Kim

Research output: Contribution to journalArticle

Abstract

It has long been considered that intron-containing (spliced) mRNAs are translationally more active than intronless mRNAs (identical mRNA not produced by splicing). The splicing-dependent translational enhancement is mediated, in part, by the exon junction complex (EJC). Nonetheless, the molecular mechanism by which each EJC component contributes to the translational enhancement remains unclear. Here, we demonstrate the previously unappreciated role of eukaryotic translation initiation factor 4AIII (eIF4AIII), a component of EJC, in the translation of mRNAs bound by the nuclear cap-binding complex (CBC), a heterodimer of cap-binding protein 80 (CBP80) and CBP20. eIF4AIII is recruited to the 5'-end of mRNAs bound by the CBC by direct interaction with the CBC-dependent translation initiation factor (CTIF); this recruitment of eIF4AIII is independent of the presence of introns (deposited EJCs after splicing). Polysome fractionation, tethering experiments, and in vitro reconstitution experiments using recombinant proteins show that eIF4AIII promotes efficient unwinding of secondary structures in 5'UTR, and consequently enhances CBC-dependent translation in vivo and in vitro. Therefore, our data provide evidence that eIF4AIII is a specific translation initiation factor for CBC-dependent translation.

Original languageEnglish
Pages (from-to)E4577-E4586
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number43
DOIs
Publication statusPublished - 2014 Oct 28

Fingerprint

Eukaryotic Initiation Factor-4A
5' Untranslated Regions
Messenger RNA
Exons
Peptide Initiation Factors
Introns
RNA Cap-Binding Proteins
Polyribosomes
Protein Biosynthesis
Recombinant Proteins

Keywords

  • cap-binding complex
  • CTIF
  • eIF4AIII
  • nonsense-mediated mRNA decay
  • translation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

eIF4AIII enhances translation of nuclear cap-binding complex-bound mRNAs by promoting disruption of secondary structures in 5'UTR. / Choe, Junho; Ryu, Incheol; Park, Ok H yun; Park, Joori; Cho, Hana; Yoo, Jin S eon; Chi, Sung W ook; Kim, Min K yung; Song, Hyun K yu; Kim, Yoon K i.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 43, 28.10.2014, p. E4577-E4586.

Research output: Contribution to journalArticle

Choe, Junho ; Ryu, Incheol ; Park, Ok H yun ; Park, Joori ; Cho, Hana ; Yoo, Jin S eon ; Chi, Sung W ook ; Kim, Min K yung ; Song, Hyun K yu ; Kim, Yoon K i. / eIF4AIII enhances translation of nuclear cap-binding complex-bound mRNAs by promoting disruption of secondary structures in 5'UTR. In: Proceedings of the National Academy of Sciences of the United States of America. 2014 ; Vol. 111, No. 43. pp. E4577-E4586.
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