Journal
ELIFE
Volume 5, Issue -, Pages -Publisher
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.17096
Keywords
Nanos; Pumilio; translational repression; cooperative RNA binding
Categories
Funding
- NIGMS [R01GM105707]
- NIH [NRSA 5T32GM007544]
- American Cancer Society [RSG-13-080-01-RMC]
- NSF [DGE 1256260]
- Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (TMTH)
- US Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38]
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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.
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