Drosophila Nanos acts as a molecular clamp that modulates the RNA-binding and repression activities of Pumilio
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.
- Authors:
-
[4]
- Department of Biological Chemistry, University of Michigan, Ann Arbor, United States
- Epigenetics and Stem Cell Biology Laboratory, National Institutes of Health, Research Triangle Park, United States, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, United States
- Department of Biological Sciences, University of Texas at Dallas, Richardson, United States
- Department of Biological Chemistry, University of Michigan, Ann Arbor, United States, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, United States
- Publication Date:
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1280193
- Alternate Identifier(s):
- OSTI ID: 1280194
- Grant/Contract Number:
- W-31-109-Eng-38
- Resource Type:
- Published Article
- Journal Name:
- eLife
- Additional Journal Information:
- Journal Name: eLife Journal Volume: 5; Journal ID: ISSN 2050-084X
- Publisher:
- eLife Sciences Publications, Ltd.
- Country of Publication:
- United States
- Language:
- English
Citation Formats
Weidmann, Chase A., Qiu, Chen, Arvola, René M., Lou, Tzu-Fang, Killingsworth, Jordan, Campbell, Zachary T., Tanaka Hall, Traci M., and Goldstrohm, Aaron C. Drosophila Nanos acts as a molecular clamp that modulates the RNA-binding and repression activities of Pumilio. United States: N. p., 2016.
Web. doi:10.7554/eLife.17096.
Weidmann, Chase A., Qiu, Chen, Arvola, René M., Lou, Tzu-Fang, Killingsworth, Jordan, Campbell, Zachary T., Tanaka Hall, Traci M., & Goldstrohm, Aaron C. Drosophila Nanos acts as a molecular clamp that modulates the RNA-binding and repression activities of Pumilio. United States. https://doi.org/10.7554/eLife.17096
Weidmann, Chase A., Qiu, Chen, Arvola, René M., Lou, Tzu-Fang, Killingsworth, Jordan, Campbell, Zachary T., Tanaka Hall, Traci M., and Goldstrohm, Aaron C. Tue .
"Drosophila Nanos acts as a molecular clamp that modulates the RNA-binding and repression activities of Pumilio". United States. https://doi.org/10.7554/eLife.17096.
@article{osti_1280193,
title = {Drosophila Nanos acts as a molecular clamp that modulates the RNA-binding and repression activities of Pumilio},
author = {Weidmann, Chase A. and Qiu, Chen and Arvola, René M. and Lou, Tzu-Fang and Killingsworth, Jordan and Campbell, Zachary T. and Tanaka Hall, Traci M. and Goldstrohm, Aaron C.},
abstractNote = {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.},
doi = {10.7554/eLife.17096},
journal = {eLife},
number = ,
volume = 5,
place = {United States},
year = {Tue Aug 02 00:00:00 EDT 2016},
month = {Tue Aug 02 00:00:00 EDT 2016}
}
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