eIF4AIII enhances translation of nuclear cap-binding complex？bound mRNAs by promoting disruption of secondary structures in 5′UTR
Junho Choea,1,2, Incheol Ryua,1, Ok Hyun Parka, Joori Parka, Hana Choa,3, Jin Seon Yoob, Sung Wook Chib,c, Min Kyung Kima, Hyun Kyu Songa, and Yoon Ki Kima,4
aDivision of Life Sciences, Korea University, Seoul 136-701, Republic of Korea;
bDepartment of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 135-710, Republic of Korea; and
cSamsung Research Institute for Future Medicine, Samsung Medical Center, Seoul 135-710, Republic of Korea
Proc. Natl. Acad. Sci. USA, October 13, 2014 | doi: 10.1073/pnas.1409695111
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.
eIF4AIII, cap-binding complex, translation, CTIF, nonsense-mediated mRNA decay