skip to main content

DOE PAGESDOE PAGES

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

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:
 [1] ;  [2] ;  [1] ;  [3] ;  [1] ;  [3] ;  [2] ; ORCiD logo [4]
  1. Department of Biological Chemistry, University of Michigan, Ann Arbor, United States
  2. 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
  3. Department of Biological Sciences, University of Texas at Dallas, Richardson, United States
  4. 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:
Grant/Contract Number:
W-31-109-Eng-38
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.
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
English
OSTI Identifier:
1280193
Alternate Identifier(s):
OSTI ID: 1280194