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Proc Natl Acad Sci U S A
2011 Sep 20;10838:15870-5. doi: 10.1073/pnas.1105151108.
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Targeted translational regulation using the PUF protein family scaffold.
Cooke A
,
Prigge A
,
Opperman L
,
Wickens M
.
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Regulatory complexes formed on mRNAs control translation, stability, and localization. These complexes possess two activities: one that binds RNA and another--the effector--that elicits a biological function. The Pumilio and FBF (PUF) protein family of RNA binding proteins provides a versatile scaffold to design and select proteins with new specificities. Here, the PUF scaffold is used to target translational activation and repression of specific mRNAs, and to induce specific poly(A) addition and removal. To do so, we linked PUF scaffold proteins to a translational activator, GLD2, or a translational repressor, CAF1. The chimeric proteins activate or repress the targeted mRNAs in Xenopus oocytes, and elicit poly(A) addition or removal. The magnitude of translational control relates directly to the affinity of the RNA-protein complex over a 100-fold range of K(d). The chimeric proteins act on both reporter and endogenous mRNAs: an mRNA that normally is deadenylated during oocyte maturation instead receives poly(A) in the presence of an appropriate chimera. The PUF-effector strategy enables the design of proteins that affect translation and stability of specific mRNAs in vivo.
Beerli,
Engineering polydactyl zinc-finger transcription factors.
2002,
Pubmed
Benoit,
PAP- and GLD-2-type poly(A) polymerases are required sequentially in cytoplasmic polyadenylation and oogenesis in Drosophila.
2008,
Pubmed
Charlesworth,
Cytoplasmic polyadenylation element (CPE)- and CPE-binding protein (CPEB)-independent mechanisms regulate early class maternal mRNA translational activation in Xenopus oocytes.
2004,
Pubmed
,
Xenbase
Chen,
AU-rich elements: characterization and importance in mRNA degradation.
1995,
Pubmed
Cheong,
Engineering RNA sequence specificity of Pumilio repeats.
2006,
Pubmed
Chritton,
Translational repression by PUF proteins in vitro.
2010,
Pubmed
Coller,
Tethered function assays: an adaptable approach to study RNA regulatory proteins.
2007,
Pubmed
Coller,
mRNA stabilization by poly(A) binding protein is independent of poly(A) and requires translation.
1998,
Pubmed
Condeelis,
How and why does beta-actin mRNA target?
2005,
Pubmed
Cooke,
Translational repression by deadenylases.
2010,
Pubmed
,
Xenbase
Crittenden,
A conserved RNA-binding protein controls germline stem cells in Caenorhabditis elegans.
2002,
Pubmed
De Gregorio,
Translation driven by an eIF4G core domain in vivo.
1999,
Pubmed
Dong,
Specific and modular binding code for cytosine recognition in Pumilio/FBF (PUF) RNA-binding domains.
2011,
Pubmed
Edwards,
Structure of Pumilio reveals similarity between RNA and peptide binding motifs.
2001,
Pubmed
Fabian,
Regulation of mRNA translation and stability by microRNAs.
2010,
Pubmed
Fox,
Poly(A) removal during oocyte maturation: a default reaction selectively prevented by specific sequences in the 3' UTR of certain maternal mRNAs.
1990,
Pubmed
,
Xenbase
Fox,
Poly(A) addition during maturation of frog oocytes: distinct nuclear and cytoplasmic activities and regulation by the sequence UUUUUAU.
1989,
Pubmed
,
Xenbase
Franks,
The control of mRNA decapping and P-body formation.
2008,
Pubmed
Gebauer,
Translational control of 15-lipoxygenase and msl-2 mRNAs: single regulators or corepressor assemblies?
2001,
Pubmed
Goldstrohm,
Multifunctional deadenylase complexes diversify mRNA control.
2008,
Pubmed
Gray,
Multiple portions of poly(A)-binding protein stimulate translation in vivo.
2000,
Pubmed
,
Xenbase
Gupta,
Structures of human Pumilio with noncognate RNAs reveal molecular mechanisms for binding promiscuity.
2008,
Pubmed
Houshmandi,
Yeast Puf3 mutants reveal the complexity of Puf-RNA binding and identify a loop required for regulation of mRNA decay.
2005,
Pubmed
Kim,
Opposing polymerase-deadenylase activities regulate cytoplasmic polyadenylation.
2006,
Pubmed
,
Xenbase
Koh,
Stacking interactions in PUF-RNA complexes.
2011,
Pubmed
Koh,
A single C. elegans PUF protein binds RNA in multiple modes.
2009,
Pubmed
Kwak,
GLD2 poly(A) polymerase is required for long-term memory.
2008,
Pubmed
Kwak,
Mammalian GLD-2 homologs are poly(A) polymerases.
2004,
Pubmed
,
Xenbase
Legagneux,
Substrate-specific regulation of RNA deadenylation in Xenopus embryo and activated egg extracts.
1995,
Pubmed
,
Xenbase
Miller,
Basis of altered RNA-binding specificity by PUF proteins revealed by crystal structures of yeast Puf4p.
2008,
Pubmed
Minshall,
A conserved role of a DEAD box helicase in mRNA masking.
2001,
Pubmed
,
Xenbase
Opperman,
A single spacer nucleotide determines the specificities of two mRNA regulatory proteins.
2005,
Pubmed
Pabo,
Design and selection of novel Cys2His2 zinc finger proteins.
2001,
Pubmed
Paillard,
EDEN and EDEN-BP, a cis element and an associated factor that mediate sequence-specific mRNA deadenylation in Xenopus embryos.
1998,
Pubmed
,
Xenbase
Paillard,
East of EDEN was a poly(A) tail.
2003,
Pubmed
,
Xenbase
Ramirez,
Unexpected failure rates for modular assembly of engineered zinc fingers.
2008,
Pubmed
Rouhana,
Vertebrate GLD2 poly(A) polymerases in the germline and the brain.
2005,
Pubmed
,
Xenbase
Sheets,
Two phases in the addition of a poly(A) tail.
1989,
Pubmed
Tucker,
The transcription factor associated Ccr4 and Caf1 proteins are components of the major cytoplasmic mRNA deadenylase in Saccharomyces cerevisiae.
2001,
Pubmed
Varnum,
Deadenylation of maternal mRNAs during Xenopus oocyte maturation does not require specific cis-sequences: a default mechanism for translational control.
1990,
Pubmed
,
Xenbase
Wang,
Engineering splicing factors with designed specificities.
2009,
Pubmed
Wang,
A regulatory cytoplasmic poly(A) polymerase in Caenorhabditis elegans.
2002,
Pubmed
Wang,
Structural basis for specific recognition of multiple mRNA targets by a PUF regulatory protein.
2009,
Pubmed
Wang,
Modular recognition of RNA by a human pumilio-homology domain.
2002,
Pubmed
,
Xenbase
Wang,
Crystal structure of a Pumilio homology domain.
2001,
Pubmed
Wickens,
In the beginning is the end: regulation of poly(A) addition and removal during early development.
1990,
Pubmed
Wickens,
A PUF family portrait: 3'UTR regulation as a way of life.
2002,
Pubmed
Wormington,
Preparation of synthetic mRNAs and analyses of translational efficiency in microinjected Xenopus oocytes.
1991,
Pubmed
,
Xenbase
Zhang,
A conserved RNA-binding protein that regulates sexual fates in the C. elegans hermaphrodite germ line.
1997,
Pubmed
Zhang,
Synthetic zinc finger transcription factor action at an endogenous chromosomal site. Activation of the human erythropoietin gene.
2000,
Pubmed
Zhu,
A 5' cytosine binding pocket in Puf3p specifies regulation of mitochondrial mRNAs.
2009,
Pubmed