Drosophila Nanos acts as a molecular clamp that modulates the RNA-binding and repression activities of Pumilio

  1. Chase A Weidmann
  2. Chen Qiu
  3. René M Arvola
  4. Tzu-Fang Lou
  5. Jordan Killingsworth
  6. Zachary T Campbell
  7. Traci M Tanaka Hall  Is a corresponding author
  8. Aaron C Goldstrohm  Is a corresponding author
  1. University of Michigan, United States
  2. National Institutes of Health, United States
  3. University of Texas at Dallas, United States

Abstract

Collaboration among the multitude of RNA-binding proteins (RBPs) is ubiquitous, yet our understanding of these key regulatory complexes has been limited to single RBPs. We investigated combinatorial translational regulation by Drosophila Pumilio (Pum) and Nanos (Nos), which control development, fertility, and neuronal functions. Our results show how the specificity of one RBP (Pum) is modulated by cooperative RNA recognition with a second RBP (Nos) to synergistically repress mRNAs. Crystal structures of Nos-Pum-RNA complexes reveal that Nos embraces Pum and RNA, contributes sequence-specific contacts, and increases Pum RNA-binding affinity. Nos shifts the recognition sequence and promotes repression complex formation on mRNAs that are not stably bound by Pum alone, explaining the preponderance of sub-optimal Pum sites regulated in vivo. Our results illuminate the molecular mechanism of a regulatory switch controlling crucial gene expression programs, and provide a framework for understanding how the partnering of RBPs evokes changes in binding specificity that underlie regulatory network dynamics.

Article and author information

Author details

  1. Chase A Weidmann

    Department of Biological Chemistry, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Chen Qiu

    Epigenetics and Stem Cell Biology Laboratory, National Institutes of Health, Research Triangle Park, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. René M Arvola

    Department of Biological Chemistry, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Tzu-Fang Lou

    Department of Biological Sciences, University of Texas at Dallas, Richardson, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Jordan Killingsworth

    Department of Biological Chemistry, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Zachary T Campbell

    Department of Biological Sciences, University of Texas at Dallas, Richardson, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Traci M Tanaka Hall

    Epigenetics and Stem Cell Biology Laboratory, National Institutes of Health, Research Triangle Park, United States
    For correspondence
    hall4@niehs.nih.gov
    Competing interests
    The authors declare that no competing interests exist.
  8. Aaron C Goldstrohm

    Department of Biological Chemistry, University of Michigan, Ann Arbor, United States
    For correspondence
    agoldstr@umn.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1867-8763

Funding

National Institutes of Health (NIGMS R01GM105707)

  • Chase A Weidmann
  • René M Arvola
  • Jordan Killingsworth
  • Aaron C Goldstrohm

National Institutes of Health (NRSA 5T32GM007544)

  • Chase A Weidmann
  • René M Arvola

American Cancer Society (RSG-13-080-01-RMC)

  • Chase A Weidmann
  • Aaron C Goldstrohm

National Institute of Environmental Health Sciences (Intramural Research Program)

  • Chen Qiu
  • Traci M Tanaka Hall

U.S. Department of Energy (W-31-109-Eng-38)

  • Chen Qiu
  • Traci M Tanaka Hall

National Science Foundation (DGE 1256260)

  • René M Arvola

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

Reviewing Editor

  1. Leemor Joshua-Tor, Cold Spring Harbor Laboratory, United States

Publication history

  1. Received: April 20, 2016
  2. Accepted: August 1, 2016
  3. Accepted Manuscript published: August 2, 2016 (version 1)
  4. Version of Record published: August 23, 2016 (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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  1. Chase A Weidmann
  2. Chen Qiu
  3. René M Arvola
  4. Tzu-Fang Lou
  5. Jordan Killingsworth
  6. Zachary T Campbell
  7. Traci M Tanaka Hall
  8. Aaron C Goldstrohm
(2016)
Drosophila Nanos acts as a molecular clamp that modulates the RNA-binding and repression activities of Pumilio
eLife 5:e17096.
https://doi.org/10.7554/eLife.17096
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