EIF4AIII enhances translation of nuclear cap-binding complex-bound mRNAs by promoting disruption of secondary structures in UTR

Junho Choe, Incheol Ryu, Ok Hyun Park, Joori Park, Hana Cho, Jin Seon Yoo, Sung Wook Chi, Min Kyung Kim, Hyun Kyu Song, Yoon Ki Kim

Research output: Contribution to journalArticle

30 Citations (Scopus)

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 CBCdependent 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
Untranslated Regions
Messenger RNA
Exons
Peptide Initiation Factors
Introns
RNA Cap-Binding Proteins
Polyribosomes
Protein Biosynthesis
Recombinant Proteins

Cite this

EIF4AIII enhances translation of nuclear cap-binding complex-bound mRNAs by promoting disruption of secondary structures in UTR. / Choe, Junho; Ryu, Incheol; Park, Ok Hyun; Park, Joori; Cho, Hana; Yoo, Jin Seon; Chi, Sung Wook; Kim, Min Kyung; Song, Hyun Kyu; Kim, Yoon Ki.

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

@article{2dffefccac224295b6e0a644e91a1329,
title = "EIF4AIII enhances translation of nuclear cap-binding complex-bound mRNAs by promoting disruption of secondary structures in UTR",
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 CBCdependent 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.",
author = "Junho Choe and Incheol Ryu and Park, {Ok Hyun} and Joori Park and Hana Cho and Yoo, {Jin Seon} and Chi, {Sung Wook} and Kim, {Min Kyung} and Song, {Hyun Kyu} and Kim, {Yoon Ki}",
year = "2014",
month = "10",
day = "28",
doi = "10.1073/pnas.1409695111/-/DCSupplemental",
language = "English",
volume = "111",
pages = "E4577--E4586",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "43",

}

TY - JOUR

T1 - EIF4AIII enhances translation of nuclear cap-binding complex-bound mRNAs by promoting disruption of secondary structures in UTR

AU - Choe, Junho

AU - Ryu, Incheol

AU - Park, Ok Hyun

AU - Park, Joori

AU - Cho, Hana

AU - Yoo, Jin Seon

AU - Chi, Sung Wook

AU - Kim, Min Kyung

AU - Song, Hyun Kyu

AU - Kim, Yoon Ki

PY - 2014/10/28

Y1 - 2014/10/28

N2 - 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 CBCdependent 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.

AB - 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 CBCdependent 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.

UR - http://www.scopus.com/inward/record.url?scp=84908565789&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84908565789&partnerID=8YFLogxK

U2 - 10.1073/pnas.1409695111/-/DCSupplemental

DO - 10.1073/pnas.1409695111/-/DCSupplemental

M3 - Article

C2 - 25313076

AN - SCOPUS:84908565789

VL - 111

SP - E4577-E4586

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 43

ER -