RT Journal Article
SR Electronic
T1 eIF4A is stimulated by the pre-initiation complex and enhances recruitment of mRNAs regardless of structural complexity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 147959
DO 10.1101/147959
A1 Paul Yourik
A1 Colin Echeverría Aitken
A1 Fujun Zhou
A1 Neha Gupta
A1 Alan G. Hinnebusch
A1 Jon R. Lorsch
YR 2017
UL http://biorxiv.org/content/early/2017/06/12/147959.abstract
AB 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 the PIC stimulates the ATPase of eIF4A, indicating that the factor acts in association with initiating ribosomal complexes rather than exclusively on isolated mRNAs. ATP hydrolysis by eIF4A accelerates the rate of recruitment for all mRNAs tested, regardless of their degree of secondary structure, indicating that the factor plays important roles beyond unwinding mRNA structure. Structures in the 5′-UTR and 3′ of the start codon synergistically inhibit mRNA recruitment, in a manner relieved by eIF4A, suggesting that the factor resolves global mRNA structure rather than just secondary structures in the 5′-UTR. We suggest that eIF4A breaks the many weak interactions formed within an mRNA that occlude the 5′-UTR and facilitates engagement of the 5′-UTR with the PIC.