Drosophila Nanos acts as a molecular clamp that modulates the RNA-binding and repression activities of Pumilio
- University of Michigan, United States
- National Institutes of Health, United States
- 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
Aaron C Goldstrohm
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.
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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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
