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PDBsum entry 2adc
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RNA binding protein/RNA
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PDB id
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2adc
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* Residue conservation analysis
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PDB id:
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RNA binding protein/RNA
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Title:
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Solution structure of polypyrimidine tract binding protein rbd34 complexed with cucucu RNA
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Structure:
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5'-r( Cp Up Cp Up Cp U)-3'. Chain: b, c. Engineered: yes. Polypyrimidine tract-binding protein 1. Chain: a. Fragment: rbd34. Synonym: ptb, heterogeneous nuclear ribonucleoprotein i, hnrnp i, 57 kda RNA-binding protein pptb-1. Engineered: yes
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Source:
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Synthetic: yes. Other_details: this sequence occurs naturally in humans.. Homo sapiens. Human. Organism_taxid: 9606. Gene: ptb-1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
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NMR struc:
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20 models
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Authors:
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F.C.Oberstrass,S.D.Auweter,M.Erat,Y.Hargous,A.Henning,P.Wenter, L.Reymond,S.Pitsch,D.L.Black,F.H.T.Allain
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Key ref:
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F.C.Oberstrass
et al.
(2005).
Structure of PTB bound to RNA: specific binding and implications for splicing regulation.
Science,
309,
2054-2057.
PubMed id:
DOI:
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Date:
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20-Jul-05
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Release date:
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04-Oct-05
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PROCHECK
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Headers
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References
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P26599
(PTBP1_HUMAN) -
Polypyrimidine tract-binding protein 1 from Homo sapiens
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Seq:
Struc:
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557 a.a.
208 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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C-U-C-U-C-U
6 bases
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C-U-C-U-C-U
6 bases
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DOI no:
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Science
309:2054-2057
(2005)
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PubMed id:
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Structure of PTB bound to RNA: specific binding and implications for splicing regulation.
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F.C.Oberstrass,
S.D.Auweter,
M.Erat,
Y.Hargous,
A.Henning,
P.Wenter,
L.Reymond,
B.Amir-Ahmady,
S.Pitsch,
D.L.Black,
F.H.Allain.
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ABSTRACT
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The polypyrimidine tract binding protein (PTB) is a 58-kilodalton RNA binding
protein involved in multiple aspects of messenger RNA metabolism, including the
repression of alternative exons. We have determined the solution structures of
the four RNA binding domains (RBDs) of PTB, each bound to a CUCUCU
oligonucleotide. Each RBD binds RNA with a different binding specificity. RBD3
and RBD4 interact, resulting in an antiparallel orientation of their bound RNAs.
Thus, PTB will induce RNA looping when bound to two separated pyrimidine tracts
within the same RNA. This leads to structural models for how PTB functions as an
alternative-splicing repressor.
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Selected figure(s)
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Figure 1.
Fig. 1. Overlay of the structural ensemble and view of the most
representative structure for each RBD of PTB in complex with
RNA. Overlay of the 20 lowest energy structures of PTB RBD1 (A,
top), RBD2 (B, top), RBD3 (C, top), and RBD4 (D, top) in complex
with CUCUCU, the protein backbone, and the RNA heavy atoms of
the bound nucleotides are shown. View of the most representative
structure of each RBD in complex with CUCUCU: RBD1 (A, bottom),
RBD2 (B, bottom), RBD3 (C, bottom) and RBD4 (D, bottom).
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Figure 3.
Fig. 3. PTB RBD3 and RBD4 interdomain interactions. (A) Overlay
of the 20 lowest energy structures of PTB RBD34 in complex with
CUCUCU. RBD3 is in blue, RBD4 in green, the interdomain linker
in red, and the RNA in yellow. (B) View of the most
representative structure. The side chains contributing to the
interdomain interaction are shown by black sticks and by black
dots representing their surfaces.
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The above figures are
reprinted
by permission from the AAAs:
Science
(2005,
309,
2054-2057)
copyright 2005.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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Y.Wang,
X.Xiao,
J.Zhang,
R.Choudhury,
A.Robertson,
K.Li,
M.Ma,
C.B.Burge,
and
Z.Wang
(2013).
A complex network of factors with overlapping affinities represses splicing through intronic elements.
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Nat Struct Mol Biol,
20,
36-45.
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A.Cléry,
S.Jayne,
N.Benderska,
C.Dominguez,
S.Stamm,
and
F.H.Allain
(2011).
Molecular basis of purine-rich RNA recognition by the human SR-like protein Tra2-β1.
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Nat Struct Mol Biol,
18,
443-450.
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PDB code:
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B.M.Lunde,
M.Hörner,
and
A.Meinhart
(2011).
Structural insights into cis element recognition of non-polyadenylated RNAs by the Nab3-RRM.
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Nucleic Acids Res,
39,
337-346.
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PDB codes:
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B.R.Graveley
(2011).
Getting in the loop: new insights into the mechanism of poly(A) site recognition.
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Structure,
19,
279-281.
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C.Dominguez,
M.Schubert,
O.Duss,
S.Ravindranathan,
and
F.H.Allain
(2011).
Structure determination and dynamics of protein-RNA complexes by NMR spectroscopy.
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Prog Nucl Magn Reson Spectrosc,
58,
1.
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J.C.Lin,
and
W.Y.Tarn
(2011).
RBM4 down-regulates PTB and antagonizes its activity in muscle cell-specific alternative splicing.
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J Cell Biol,
193,
509-520.
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J.Sztuba-Solińska,
V.Stollar,
and
J.J.Bujarski
(2011).
Subgenomic messenger RNAs: mastering regulation of (+)-strand RNA virus life cycle.
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Virology,
412,
245-255.
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K.B.Cook,
H.Kazan,
K.Zuberi,
Q.Morris,
and
T.R.Hughes
(2011).
RBPDB: a database of RNA-binding specificities.
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Nucleic Acids Res,
39,
D301-D308.
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Q.Yang,
M.Coseno,
G.M.Gilmartin,
and
S.Doublié
(2011).
Crystal structure of a human cleavage factor CFI(m)25/CFI(m)68/RNA complex provides an insight into poly(A) site recognition and RNA looping.
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Structure,
19,
368-377.
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PDB codes:
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S.Sharma,
C.Maris,
F.H.Allain,
and
D.L.Black
(2011).
U1 snRNA directly interacts with polypyrimidine tract-binding protein during splicing repression.
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Mol Cell,
41,
579-588.
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Y.Bai,
S.K.Srivastava,
J.H.Chang,
J.L.Manley,
and
L.Tong
(2011).
Structural basis for dimerization and activity of human PAPD1, a noncanonical poly(A) polymerase.
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Mol Cell,
41,
311-320.
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PDB code:
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Y.Yang,
L.Zhan,
W.Zhang,
F.Sun,
W.Wang,
N.Tian,
J.Bi,
H.Wang,
D.Shi,
Y.Jiang,
Y.Zhang,
and
Y.Jin
(2011).
RNA secondary structure in mutually exclusive splicing.
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Nat Struct Mol Biol,
18,
159-168.
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C.M.Maynard,
and
K.B.Hall
(2010).
Interactions between PTB RRMs induce slow motions and increase RNA binding affinity.
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J Mol Biol,
397,
260-277.
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D.Cherny,
C.Gooding,
G.E.Eperon,
M.B.Coelho,
C.R.Bagshaw,
C.W.Smith,
and
I.C.Eperon
(2010).
Stoichiometry of a regulatory splicing complex revealed by single-molecule analyses.
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EMBO J,
29,
2161-2172.
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H.Kazan,
D.Ray,
E.T.Chan,
T.R.Hughes,
and
Q.Morris
(2010).
RNAcontext: a new method for learning the sequence and structure binding preferences of RNA-binding proteins.
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PLoS Comput Biol,
6,
e1000832.
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J.A.Chao,
Y.Patskovsky,
V.Patel,
M.Levy,
S.C.Almo,
and
R.H.Singer
(2010).
ZBP1 recognition of beta-actin zipcode induces RNA looping.
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Genes Dev,
24,
148-158.
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PDB code:
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J.König,
K.Zarnack,
G.Rot,
T.Curk,
M.Kayikci,
B.Zupan,
D.J.Turner,
N.M.Luscombe,
and
J.Ule
(2010).
iCLIP reveals the function of hnRNP particles in splicing at individual nucleotide resolution.
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Nat Struct Mol Biol,
17,
909-915.
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L.Skrisovska,
M.Schubert,
and
F.H.Allain
(2010).
Recent advances in segmental isotope labeling of proteins: NMR applications to large proteins and glycoproteins.
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J Biomol NMR,
46,
51-65.
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L.Yang,
L.Gu,
Z.Li,
and
M.Zhou
(2010).
Translation of TRAF1 is regulated by IRES-dependent mechanism and stimulated by vincristine.
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Nucleic Acids Res,
38,
4503-4513.
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M.B.Warf,
and
J.A.Berglund
(2010).
Role of RNA structure in regulating pre-mRNA splicing.
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Trends Biochem Sci,
35,
169-178.
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M.Llorian,
S.Schwartz,
T.A.Clark,
D.Hollander,
L.Y.Tan,
R.Spellman,
A.Gordon,
A.C.Schweitzer,
P.de la Grange,
G.Ast,
and
C.W.Smith
(2010).
Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB.
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Nat Struct Mol Biol,
17,
1114-1123.
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M.Robida,
V.Sridharan,
S.Morgan,
T.Rao,
and
R.Singh
(2010).
Drosophila polypyrimidine tract-binding protein is necessary for spermatid individualization.
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Proc Natl Acad Sci U S A,
107,
12570-12575.
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P.Kafasla,
N.Morgner,
C.V.Robinson,
and
R.J.Jackson
(2010).
Polypyrimidine tract-binding protein stimulates the poliovirus IRES by modulating eIF4G binding.
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EMBO J,
29,
3710-3722.
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Q.Yang,
G.M.Gilmartin,
and
S.Doublié
(2010).
Structural basis of UGUA recognition by the Nudix protein CFI(m)25 and implications for a regulatory role in mRNA 3' processing.
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Proc Natl Acad Sci U S A,
107,
10062-10067.
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PDB codes:
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R.Lamichhane,
G.M.Daubner,
J.Thomas-Crusells,
S.D.Auweter,
C.Manatschal,
K.S.Austin,
O.Valniuk,
F.H.Allain,
and
D.Rueda
(2010).
RNA looping by PTB: Evidence using FRET and NMR spectroscopy for a role in splicing repression.
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Proc Natl Acad Sci U S A,
107,
4105-4110.
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S.Khoshnevis,
P.Neumann,
and
R.Ficner
(2010).
Crystal structure of the RNA recognition motif of yeast translation initiation factor eIF3b reveals differences to human eIF3b.
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PLoS One,
5,
0.
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PDB codes:
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V.A.Barron,
H.Zhu,
M.N.Hinman,
A.N.Ladd,
and
H.Lou
(2010).
The neurofibromatosis type I pre-mRNA is a novel target of CELF protein-mediated splicing regulation.
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Nucleic Acids Res,
38,
253-264.
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X.Li,
G.Quon,
H.D.Lipshitz,
and
Q.Morris
(2010).
Predicting in vivo binding sites of RNA-binding proteins using mRNA secondary structure.
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RNA,
16,
1096-1107.
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Y.Barash,
J.A.Calarco,
W.Gao,
Q.Pan,
X.Wang,
O.Shai,
B.J.Blencowe,
and
B.J.Frey
(2010).
Deciphering the splicing code.
|
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Nature,
465,
53-59.
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A.Corrionero,
and
J.Valcárcel
(2009).
RNA processing: Redrawing the map of charted territory.
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Mol Cell,
36,
918-919.
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C.Clerte,
and
K.B.Hall
(2009).
The domains of polypyrimidine tract binding protein have distinct RNA structural preferences.
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Biochemistry,
48,
2063-2074.
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D.C.Reid,
B.L.Chang,
S.I.Gunderson,
L.Alpert,
W.A.Thompson,
and
W.G.Fairbrother
(2009).
Next-generation SELEX identifies sequence and structural determinants of splicing factor binding in human pre-mRNA sequence.
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RNA,
15,
2385-2397.
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D.Ray,
H.Kazan,
E.T.Chan,
L.P.Castillo,
S.Chaudhry,
S.Talukder,
B.J.Blencowe,
Q.Morris,
and
T.R.Hughes
(2009).
Rapid and systematic analysis of the RNA recognition specificities of RNA-binding proteins.
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Nat Biotechnol,
27,
667-670.
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F.Besse,
S.López de Quinto,
V.Marchand,
A.Trucco,
and
A.Ephrussi
(2009).
Drosophila PTB promotes formation of high-order RNP particles and represses oskar translation.
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Genes Dev,
23,
195-207.
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J.A.Dembowski,
and
P.J.Grabowski
(2009).
The CUGBP2 splicing factor regulates an ensemble of branchpoints from perimeter binding sites with implications for autoregulation.
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PLoS Genet,
5,
e1000595.
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J.Yang,
C.Y.Chan,
B.Jiang,
X.Yu,
G.Z.Zhu,
Y.Chen,
J.Barnard,
and
W.Mei
(2009).
hnRNP I Inhibits Notch Signaling and Regulates Intestinal Epithelial Homeostasis in the Zebrafish.
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PLoS Genet,
5,
e1000363.
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K.Masuda,
K.Abdelmohsen,
and
M.Gorospe
(2009).
RNA-binding proteins implicated in the hypoxic response.
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J Cell Mol Med,
13,
2759-2769.
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K.Tsuda,
K.Kuwasako,
M.Takahashi,
T.Someya,
M.Inoue,
T.Terada,
N.Kobayashi,
M.Shirouzu,
T.Kigawa,
A.Tanaka,
S.Sugano,
P.Güntert,
Y.Muto,
and
S.Yokoyama
(2009).
Structural basis for the sequence-specific RNA-recognition mechanism of human CUG-BP1 RRM3.
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Nucleic Acids Res,
37,
5151-5166.
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PDB codes:
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M.Z.Stern,
S.K.Gupta,
M.Salmon-Divon,
T.Haham,
O.Barda,
S.Levi,
C.Wachtel,
T.W.Nilsen,
and
S.Michaeli
(2009).
Multiple roles for polypyrimidine tract binding (PTB) proteins in trypanosome RNA metabolism.
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RNA,
15,
648-665.
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S.Vavassori,
and
L.R.Covey
(2009).
Post-transcriptional regulation in lymphocytes: the case of CD154.
|
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RNA Biol,
6,
259-265.
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Y.Bian,
A.Masuda,
T.Matsuura,
M.Ito,
K.Okushin,
A.G.Engel,
and
K.Ohno
(2009).
Tannic acid facilitates expression of the polypyrimidine tract binding protein and alleviates deleterious inclusion of CHRNA1 exon P3A due to an hnRNP H-disrupting mutation in congenital myasthenic syndrome.
|
| |
Hum Mol Genet,
18,
1229-1237.
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Y.Xue,
Y.Zhou,
T.Wu,
T.Zhu,
X.Ji,
Y.S.Kwon,
C.Zhang,
G.Yeo,
D.L.Black,
H.Sun,
X.D.Fu,
and
Y.Zhang
(2009).
Genome-wide analysis of PTB-RNA interactions reveals a strategy used by the general splicing repressor to modulate exon inclusion or skipping.
|
| |
Mol Cell,
36,
996.
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A.Cléry,
M.Blatter,
and
F.H.Allain
(2008).
RNA recognition motifs: boring? Not quite.
|
| |
Curr Opin Struct Biol,
18,
290-298.
|
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E.T.Wang,
R.Sandberg,
S.Luo,
I.Khrebtukova,
L.Zhang,
C.Mayr,
S.F.Kingsmore,
G.P.Schroth,
and
C.B.Burge
(2008).
Alternative isoform regulation in human tissue transcriptomes.
|
| |
Nature,
456,
470-476.
|
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F.Robinson,
R.J.Jackson,
and
C.W.Smith
(2008).
Expression of human nPTB is limited by extreme suboptimal codon content.
|
| |
PLoS ONE,
3,
e1801.
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G.Toba,
and
K.White
(2008).
The third RNA recognition motif of Drosophila ELAV protein has a role in multimerization.
|
| |
Nucleic Acids Res,
36,
1390-1399.
|
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G.V.Crichlow,
H.Zhou,
H.H.Hsiao,
K.B.Frederick,
M.Debrosse,
Y.Yang,
E.J.Folta-Stogniew,
H.J.Chung,
C.Fan,
E.M.De la Cruz,
D.Levens,
E.Lolis,
and
D.Braddock
(2008).
Dimerization of FIR upon FUSE DNA binding suggests a mechanism of c-myc inhibition.
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| |
EMBO J,
27,
277-289.
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PDB code:
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H.Zhu,
M.N.Hinman,
R.A.Hasman,
P.Mehta,
and
H.Lou
(2008).
Regulation of neuron-specific alternative splicing of neurofibromatosis type 1 pre-mRNA.
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| |
Mol Cell Biol,
28,
1240-1251.
|
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J.F.Porter,
S.Vavassori,
and
L.R.Covey
(2008).
A polypyrimidine tract-binding protein-dependent pathway of mRNA stability initiates with CpG activation of primary B cells.
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| |
J Immunol,
181,
3336-3345.
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J.L.Jenkins,
H.Shen,
M.R.Green,
and
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RNA,
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PDB codes:
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RNA,
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PDB codes:
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Mol Cell,
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PDB codes:
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F.Vitali,
A.Henning,
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PDB code:
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PDB code:
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PDB codes:
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RNA-binding domain proteins in Kinetoplastids: a comparative analysis.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
|
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