title: eIF4AIII enhances translation of nuclear cap-binding complex-bound mRNAs by promoting disruption of secondary structures in 5'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 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.
authors.affiliation: Division of Life Sciences, Korea University, Seoul 136-701, Republic of Korea;
authors.forename: Junho
authors.initials: J
authors.lastname: Choe
authors.affiliation: Division of Life Sciences, Korea University, Seoul 136-701, Republic of Korea;
authors.forename: Incheol
authors.initials: I
authors.lastname: Ryu
authors.affiliation: Division of Life Sciences, Korea University, Seoul 136-701, Republic of Korea;
authors.forename: Ok Hyun
authors.initials: OH
authors.lastname: Park
authors.affiliation: Division of Life Sciences, Korea University, Seoul 136-701, Republic of Korea;
authors.forename: Joori
authors.initials: J
authors.lastname: Park
authors.affiliation: Division of Life Sciences, Korea University, Seoul 136-701, Republic of Korea;
authors.forename: Hana
authors.initials: H
authors.lastname: Cho
authors.affiliation: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 135-710, Republic of Korea; and.
authors.forename: Jin Seon
authors.initials: JS
authors.lastname: Yoo
authors.affiliation: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 135-710, Republic of Korea; and Samsung Research Institute for Future Medicine, Samsung Medical Center, Seoul 135-710, Republic of Korea.
authors.forename: Sung Wook
authors.initials: SW
authors.lastname: Chi
authors.affiliation: Division of Life Sciences, Korea University, Seoul 136-701, Republic of Korea;
authors.forename: Min Kyung
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Division of Life Sciences, Korea University, Seoul 136-701, Republic of Korea;
authors.forename: Hyun Kyu
authors.initials: HK
authors.lastname: Song
authors.affiliation: Division of Life Sciences, Korea University, Seoul 136-701, Republic of Korea; yk-kim@korea.ac.kr.
authors.forename: Yoon Ki
authors.initials: YK
authors.lastname: Kim
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics*; D002467:Cell Nucleus / Q000378:metabolism*; D004261:DNA Replication; D015536:Down-Regulation; D039601:Eukaryotic Initiation Factor-4A / Q000378:metabolism*; D039642:Eukaryotic Initiation Factors / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D007438:Introns / Q000235:genetics; D008954:Models, Biological; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D014176:Protein Biosynthesis; D012315:RNA Caps / Q000378:metabolism*; D012326:RNA Splicing / Q000235:genetics; D020871:RNA Stability / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D020121:5' Untranslated Regions; C579433:CTIF protein, human; D039642:Eukaryotic Initiation Factors; D006657:Histones; D012315:RNA Caps; D012333:RNA, Messenger; D011994:Recombinant Proteins; D039601:Eukaryotic Initiation Factor-4A
keywords: CTIF; cap-binding complex; eIF4AIII; nonsense-mediated mRNA decay; translation