eIF4AIII enhances translation of nuclear cap-binding complex–bound mRNAs by promoting disruption of secondary structures in 5′UTR
| Autor: | Ok Hee Park, Hana Cho, Yoon Ki Kim, Incheol Ryu, Hyun Kyu Song, Joori Park, Sung W ook Chi, Jun-Ho Choe, Min K yung Kim, Jin S eon Yoo |
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| Rok vydání: | 2014 |
| Předmět: |
DNA Replication
RNA Caps Five prime untranslated region RNA Splicing RNA Stability Down-Regulation Biology Models Biological Histones Eukaryotic translation Eukaryotic initiation factor parasitic diseases Humans Initiation factor RNA Messenger Eukaryotic Initiation Factors Cell Nucleus Multidisciplinary Cap binding complex EIF4E Molecular biology Introns Recombinant Proteins Eukaryotic translation initiation factor 4 gamma Cell biology HEK293 Cells PNAS Plus Protein Biosynthesis Eukaryotic Initiation Factor-4A Nucleic Acid Conformation Exon junction complex 5' Untranslated Regions HeLa Cells Protein Binding |
| Zdroj: | Proceedings of the National Academy of Sciences. 111 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1409695111 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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