1. Biochemistry and Chemical Biology
  2. Structural Biology and Molecular Biophysics
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Yeast eIF4A enhances recruitment of mRNAs regardless of their structural complexity

  1. Paul Yourik
  2. Colin Echeverría Aitken
  3. Fujun Zhou
  4. Neha Gupta
  5. Alan G. Hinnebusch  Is a corresponding author
  6. Jon R Lorsch  Is a corresponding author
  1. National Institutes of Health, United States
Research Article
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Cite this article as: eLife 2017;6:e31476 doi: 10.7554/eLife.31476

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 eIF4A’s 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.

Article and author information

Author details

  1. Paul Yourik

    Laboratory on the Mechanism and Regulation of Protein Synthesis, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
    Competing interests
    No competing interests declared.
  2. Colin Echeverría Aitken

    Laboratory on the Mechanism and Regulation of Protein Synthesis, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
    Competing interests
    No competing interests declared.
  3. Fujun Zhou

    Laboratory on the Mechanism and Regulation of Protein Synthesis, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
    Competing interests
    No competing interests declared.
  4. Neha Gupta

    Laboratory on the Mechanism and Regulation of Protein Synthesis, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
    Competing interests
    No competing interests declared.
  5. Alan G. Hinnebusch

    Laboratory of Gene Regulation and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
    For correspondence
    ahinnebusch@nih.gov
    Competing interests
    Alan G. Hinnebusch, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1627-8395
  6. Jon R Lorsch

    Laboratory on the Mechanism and Regulation of Protein Synthesis, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
    For correspondence
    jon.lorsch@nih.gov
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4521-4999

Funding

National Institutes of Health

  • Paul Yourik
  • Colin Echeverría Aitken
  • Fujun Zhou
  • Neha Gupta
  • Alan G. Hinnebusch
  • Jon R Lorsch

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Nahum Sonenberg, McGill University, Canada

Publication history

  1. Received: August 24, 2017
  2. Accepted: November 23, 2017
  3. Accepted Manuscript published: November 30, 2017 (version 1)
  4. Version of Record published: December 12, 2017 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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