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bioRxiv · 10.1101/147959

eIF4A is stimulated by the pre-initiation complex and enhances recruitment of mRNAs regardless of structural complexity

Yourik, P.·Aitken, C. E.·Zhou, F.·Gupta, N.·Hinnebusch, A. G.·Lorsch, J. R.
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Abstract

eIF4A is a DEAD-box RNA-dependent ATPase thought to unwind RNA secondary structure in the 5'-untranslated regions (UTRs) of mRNAs to promote their recruitment to the eukaryotic translation pre-initiation complex (PIC). We show that eIF4As ATPase activity is markedly stimulated in the presence of the PIC, independently of eIF4E*eIF4G, but dependent on subunits i and g of the heteromeric eIF3 complex. Surprisingly, eIF4A accelerated the rate of recruitment of all mRNAs tested, regardless of their degree of structural complexity. Structures in the 5'-UTR and 3' of the start codon synergistically inhibit mRNA recruitment in a manner relieved by eIF4A, indicating that the factor does not act solely to melt hairpins in 5'-UTRs. Our findings that eIF4A functionally interacts with the PIC and plays important roles beyond unwinding 5-UTR structure is consistent with a recent proposal that eIF4A modulates the conformation of the 40S ribosomal subunit to promote mRNA recruitment.

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Yourik, P., Aitken, C. E., Zhou, F., Gupta, N., Hinnebusch, A. G., Lorsch, J. R.. 2017-06-13. eIF4A is stimulated by the pre-initiation complex and enhances recruitment of mRNAs regardless of structural complexity. https://doi.org/10.1101/147959

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