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

Journal Article · · eLife
DOI:https://doi.org/10.7554/eLife.17096· OSTI ID:1280193
 [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
+ Show Author Affiliations

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.

Sponsoring Organization:
USDOE
Grant/Contract Number:
W-31-109-Eng-38
OSTI ID:
1280193
Alternate ID(s):
OSTI ID: 1280194
Journal Information:
eLife, Journal Name: eLife Vol. 5; ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.Copyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 50 works
Citation information provided by
Web of Science

References (60)

Structure of the HIV-1 Nucleocapsid Protein Bound to the SL3 -RNA Recognition Element journal January 1998
RNA regulatory elements mediate control of Drosophila body pattern by the posterior morphogen nanos journal November 1991
Insights into RNA Biology from an Atlas of Mammalian mRNA-Binding Proteins journal June 2012
Basis of altered RNA-binding specificity by PUF proteins revealed by crystal structures of yeast Puf4p journal March 2008
A 5' cytosine binding pocket in Puf3p specifies regulation of mitochondrial mRNAs journal November 2009
Drosophila Brain Tumor is a translational repressor journal March 2001
The Translational Repressor Pumilio Regulates Presynaptic Morphology and Controls Postsynaptic Accumulation of Translation Factor eIF-4E journal November 2004
Alternate Modes of Cognate RNA Recognition by Human PUMILIO Proteins journal March 2011
MEME: discovering and analyzing DNA and protein sequence motifs journal July 2006
A CCHC metal-binding domain in Nanos is essential for translational regulation journal February 1997
Dali server: conservation mapping in 3D journal May 2010
The NHL domain of BRAT is an RNA-binding domain that directly contacts the hunchback mRNA for regulation journal April 2014
Biochemical Identification of Xenopus Pumilio as a Sequence-specific Cyclin B1 mRNA-binding Protein That Physically Interacts with a Nanos Homolog, Xcat-2, and a Cytoplasmic Polyadenylation Element-binding Protein journal March 2001
A protein-RNA specificity code enables targeted activation of an endogenous human transcript journal June 2014
Structural basis for the assembly of the Sxl–Unr translation regulatory complex journal September 2014
Divergence of Pumilio/ fem-3 mRNA Binding Factor (PUF) Protein Specificity through Variations in an RNA-binding Pocket journal December 2011
Recruitment of Nanos to hunchback mRNA by Pumilio journal October 1999
Regulation of Neuronal Excitability through Pumilio-Dependent Control of a Sodium Channel Gene journal October 2004
NANOS-3 and FBF proteins physically interact to control the sperm–oocyte switch in Caenorhabditis elegans journal September 1999
Drosophila Pumilio Protein Contains Multiple Autonomous Repression Domains That Regulate mRNAs Independently of Nanos and Brain Tumor journal November 2011
PHENIX : building new software for automated crystallographic structure determination journal October 2002
A Eukaryotic Translation Initiation Factor 4E-Binding Protein Promotes mRNA Decapping and Is Required for PUF Repression journal August 2012
The Pumilio RNA-Binding Domain Is Also a Translational Regulator journal May 1998
Crystal Structure of a Pumilio Homology Domain journal April 2001
nanos and pumilio Are Essential for Dendrite Morphogenesis in Drosophila Peripheral Neurons journal February 2004
Genome-wide identification of mRNAs associated with the translational regulator PUMILIO in Drosophila melanogaster journal March 2006
Potential role of Nanos3 in maintaining the undifferentiated spermatogonia population journal January 2008
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources journal December 2008
Maternal Pumilio acts together with Nanos in germline development in Drosophila embryos journal October 1999
A PUF family portrait: 3′UTR regulation as a way of life journal March 2002
Resources for the Comprehensive Discovery of Functional RNA Elements journal March 2016
The mRNA-Bound Proteome and Its Global Occupancy Profile on Protein-Coding Transcripts journal June 2012
Identification of a Conserved Interface between PUF and CPEB Proteins journal April 2012
Crystal structure of zinc-finger domain of Nanos and its functional implications journal October 2010
Nanos is the localized posterior determinant in Drosophila journal August 1991
A Protein⋅Protein Interaction Platform Involved in Recruitment of GLD-3 to the FBF⋅fem-3 mRNA Complex journal February 2013
Biochemical Characterization of the Caenorhabditis elegans FBF⋅CPB-1 Translational Regulation Complex Identifies Conserved Protein Interaction Hotspots journal February 2013
Brain tumor is a sequence-specific RNA-binding protein that directs maternal mRNA clearance during the Drosophila maternal-to-zygotic transition journal May 2015
Binding of pumilio to maternal hunchback mRNA is required for posterior patterning in drosophila embryos journal March 1995
Pumilio facilitates miRNA regulation of the E2F3 oncogene journal February 2012
Pumilio is essential for function but not for distribution of the Drosophila abdominal determinant Nanos. journal December 1992
Coot model-building tools for molecular graphics journal November 2004
The Translational Repressors Nanos and Pumilio Have Divergent Effects on Presynaptic Terminal Growth and Postsynaptic Glutamate Receptor Subunit Composition journal April 2009
Structure of Pumilio Reveals Similarity between RNA and Peptide Binding Motifs journal April 2001
The RNA binding domain of Pumilio antagonizes poly-adenosine binding protein and accelerates deadenylation journal June 2014
Distinct modes of recruitment of the CCR 4– NOT complex by Drosophila and vertebrate Nanos journal March 2016
RNA regulatory networks diversified through curvature of the PUF protein scaffold journal September 2015
A guide to design and optimization of reporter assays for 3′ untranslated region mediated regulation of mammalian messenger RNAs journal September 2013
Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists journal November 2008
A census of human RNA-binding proteins journal November 2014
Dead end1 is an essential partner of NANOS 2 for selective binding of target RNA s in male germ cell development journal November 2015
Cooperativity in RNA-Protein Interactions: Global Analysis of RNA Binding Specificity journal May 2012
Pumilio Binds para mRNA and Requires Nanos and Brat to Regulate Sodium Current in Drosophila Motoneurons journal February 2008
A conserved RNA-binding protein that regulates sexual fates in the C. elegans hermaphrodite germ line journal December 1997
Engineering splicing factors with designed specificities journal October 2009
Conservation of a Pumilio-Nanos complex from Drosophila germ plasm to human germ cells journal February 2003
The PUMILIO−RNA Interaction:  A Single RNA-Binding Domain Monomer Recognizes a Bipartite Target Sequence † journal January 1999
Translational control of maternal Cyclin B mRNA by Nanos in the Drosophila germline journal March 2007
hunchback, a gene required for segmentation of an anterior and posterior region of the Drosophila embryo journal February 1987
Modular Recognition of RNA by a Human Pumilio-Homology Domain journal August 2002

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