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PDBsum entry 1ec6
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RNA binding protein/RNA
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PDB id
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1ec6
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Contents |
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* Residue conservation analysis
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DOI no:
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Cell
100:323-332
(2000)
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PubMed id:
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Sequence-specific RNA binding by a Nova KH domain: implications for paraneoplastic disease and the fragile X syndrome.
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H.A.Lewis,
K.Musunuru,
K.B.Jensen,
C.Edo,
H.Chen,
R.B.Darnell,
S.K.Burley.
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ABSTRACT
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The structure of a Nova protein K homology (KH) domain recognizing
single-stranded RNA has been determined at 2.4 A resolution. Mammalian Nova
antigens (1 and 2) constitute an important family of regulators of RNA
metabolism in neurons, first identified using sera from cancer patients with the
autoimmune disorder paraneoplastic opsoclonus-myoclonus ataxia (POMA). The
structure of the third KH domain (KH3) of Nova-2 bound to a stem loop RNA
resembles a molecular vise, with 5'-Ura-Cyt-Ade-Cyt-3' pinioned between an
invariant Gly-X-X-Gly motif and the variable loop. Tetranucleotide recognition
is supported by an aliphatic alpha helix/beta sheet RNA-binding platform, which
mimics 5'-Ura-Gua-3' by making Watson-Crick-like hydrogen bonds with
5'-Cyt-Ade-3'. Sequence conservation suggests that fragile X mental retardation
results from perturbation of RNA binding by the FMR1 protein.
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Selected figure(s)
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Figure 2.
Figure 2. Stem Loop RNA StructuresSchematic drawings of the
stem loop crystallization RNAs in complexes 1 and 2. Nucleotides
making direct protein contacts are denoted with *. Color coding
denotes nucleotides making extensive protein contacts (Ade-11
through Cyt-15; magenta, pink, gold, green, and blue) and the
remaining nucleotides (gray).
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Figure 5.
Figure 5. 5′-Ura-Cyt-Ade-Cyt-3′ Binding by Nova-2
KH3RIBBONS drawings showing the RNA-binding surface sandwiched
between the invariant Gly-X-X-Gly motif (yellow) and the
variable loop (red). The portion of the stem loop
crystallization RNA making extensive protein contacts has been
included as a color-coded stick figure (Figure 2) with the
aliphatic residues (gray) comprising the hydrophobic α/β RNA
binding platform. (A) shows the entire complex. (B), (C), and
(D) show the environments of Ade-11 Ura-12, and Cyt-13,
respectively. (E) shows the environments of Ade-14 and Cyt-15.
The side chain of Leu-28 is denoted with *. (F) corresponds to
the views used in (D) and (E), with the overlying RNA removed,
and shows the aliphatic platform with the jaws of the molecular
vise.
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The above figures are
reprinted
by permission from Cell Press:
Cell
(2000,
100,
323-332)
copyright 2000.
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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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G.Nicastro,
M.F.García-Mayoral,
D.Hollingworth,
G.Kelly,
S.R.Martin,
P.Briata,
R.Gherzi,
and
A.Ramos
(2012).
Noncanonical G recognition mediates KSRP regulation of let-7 biogenesis.
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Nat Struct Mol Biol,
19,
1282-1286.
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PDB code:
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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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A.Chaudhury,
P.Chander,
and
P.H.Howe
(2010).
Heterogeneous nuclear ribonucleoproteins (hnRNPs) in cellular processes: Focus on hnRNP E1's multifunctional regulatory roles.
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RNA,
16,
1449-1462.
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C.Beuck,
B.R.Szymczyna,
D.E.Kerkow,
A.B.Carmel,
L.Columbus,
R.L.Stanfield,
and
J.R.Williamson
(2010).
Structure of the GLD-1 homodimerization domain: insights into STAR protein-mediated translational regulation.
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Structure,
18,
377-389.
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PDB codes:
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C.Cai,
K.Tamai,
and
K.Molyneaux
(2010).
KHDC1B is a novel CPEB binding partner specifically expressed in mouse oocytes and early embryos.
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Mol Biol Cell,
21,
3137-3148.
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I.Díaz-Moreno,
D.Hollingworth,
G.Kelly,
S.Martin,
M.García-Mayoral,
P.Briata,
R.Gherzi,
and
A.Ramos
(2010).
Orientation of the central domains of KSRP and its implications for the interaction with the RNA targets.
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Nucleic Acids Res,
38,
5193-5205.
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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.J.Wolf,
R.D.Dowell,
S.Mahony,
M.Rabani,
D.K.Gifford,
and
G.R.Fink
(2010).
Feed-forward regulation of a cell fate determinant by an RNA-binding protein generates asymmetry in yeast.
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Genetics,
185,
513-522.
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R.B.Darnell
(2010).
RNA regulation in neurologic disease and cancer.
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Cancer Res Treat,
42,
125-129.
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A.Galarneau,
and
S.Richard
(2009).
The STAR RNA binding proteins GLD-1, QKI, SAM68 and SLM-2 bind bipartite RNA motifs.
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BMC Mol Biol,
10,
47.
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C.Tu,
X.Zhou,
J.E.Tropea,
B.P.Austin,
D.S.Waugh,
D.L.Court,
and
X.Ji
(2009).
Structure of ERA in complex with the 3' end of 16S rRNA: implications for ribosome biogenesis.
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Proc Natl Acad Sci U S A,
106,
14843-14848.
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PDB codes:
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D.E.Kim,
B.Blum,
P.Bradley,
and
D.Baker
(2009).
Sampling bottlenecks in de novo protein structure prediction.
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J Mol Biol,
393,
249-260.
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F.E.Loughlin,
R.E.Mansfield,
P.M.Vaz,
A.P.McGrath,
S.Setiyaputra,
R.Gamsjaeger,
E.S.Chen,
B.J.Morris,
J.M.Guss,
and
J.P.Mackay
(2009).
The zinc fingers of the SR-like protein ZRANB2 are single-stranded RNA-binding domains that recognize 5' splice site-like sequences.
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Proc Natl Acad Sci U S A,
106,
5581-5586.
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PDB code:
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I.Díaz-Moreno,
D.Hollingworth,
T.A.Frenkiel,
G.Kelly,
S.Martin,
S.Howell,
M.García-Mayoral,
R.Gherzi,
P.Briata,
and
A.Ramos
(2009).
Phosphorylation-mediated unfolding of a KH domain regulates KSRP localization via 14-3-3 binding.
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Nat Struct Mol Biol,
16,
238-246.
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PDB code:
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J.B.Zang,
E.D.Nosyreva,
C.M.Spencer,
L.J.Volk,
K.Musunuru,
R.Zhong,
E.F.Stone,
L.A.Yuva-Paylor,
K.M.Huber,
R.Paylor,
J.C.Darnell,
and
R.B.Darnell
(2009).
A mouse model of the human Fragile X syndrome I304N mutation.
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PLoS Genet,
5,
e1000758.
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J.C.Darnell,
C.E.Fraser,
O.Mostovetsky,
and
R.B.Darnell
(2009).
Discrimination of common and unique RNA-binding activities among Fragile X mental retardation protein paralogs.
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Hum Mol Genet,
18,
3164-3177.
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J.M.Pagano,
B.M.Farley,
K.I.Essien,
and
S.P.Ryder
(2009).
RNA recognition by the embryonic cell fate determinant and germline totipotency factor MEX-3.
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Proc Natl Acad Sci U S A,
106,
20252-20257.
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M.Ruggiu,
R.Herbst,
N.Kim,
M.Jevsek,
J.J.Fak,
M.A.Mann,
G.Fischbach,
S.J.Burden,
and
R.B.Darnell
(2009).
Rescuing Z+ agrin splicing in Nova null mice restores synapse formation and unmasks a physiologic defect in motor neuron firing.
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Proc Natl Acad Sci U S A,
106,
3513-3518.
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P.Serrano,
M.A.Johnson,
A.Chatterjee,
B.W.Neuman,
J.S.Joseph,
M.J.Buchmeier,
P.Kuhn,
and
K.Wüthrich
(2009).
Nuclear magnetic resonance structure of the nucleic acid-binding domain of severe acute respiratory syndrome coronavirus nonstructural protein 3.
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J Virol,
83,
12998-13008.
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PDB code:
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A.Serganov,
and
D.J.Patel
(2008).
Towards deciphering the principles underlying an mRNA recognition code.
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Curr Opin Struct Biol,
18,
120-129.
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A.Shulman-Peleg,
M.Shatsky,
R.Nussinov,
and
H.J.Wolfson
(2008).
Prediction of interacting single-stranded RNA bases by protein-binding patterns.
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J Mol Biol,
379,
299-316.
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C.A.Chénard,
and
S.Richard
(2008).
New implications for the QUAKING RNA binding protein in human disease.
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J Neurosci Res,
86,
233-242.
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D.D.Licatalosi,
A.Mele,
J.J.Fak,
J.Ule,
M.Kayikci,
S.W.Chi,
T.A.Clark,
A.C.Schweitzer,
J.E.Blume,
X.Wang,
J.C.Darnell,
and
R.B.Darnell
(2008).
HITS-CLIP yields genome-wide insights into brain alternative RNA processing.
|
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Nature,
456,
464-469.
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E.Vanrobays,
A.Leplus,
Y.N.Osheim,
A.L.Beyer,
L.Wacheul,
and
D.L.Lafontaine
(2008).
TOR regulates the subcellular distribution of DIM2, a KH domain protein required for cotranscriptional ribosome assembly and pre-40S ribosome export.
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RNA,
14,
2061-2073.
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I.Keren,
L.Klipcan,
A.Bezawork-Geleta,
M.Kolton,
F.Shaya,
and
O.Ostersetzer-Biran
(2008).
Characterization of the Molecular Basis of Group II Intron RNA Recognition by CRS1-CRM Domains.
|
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J Biol Chem,
283,
23333-23342.
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K.E.Lukong,
K.W.Chang,
E.W.Khandjian,
and
S.Richard
(2008).
RNA-binding proteins in human genetic disease.
|
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Trends Genet,
24,
416-425.
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R.Valverde,
L.Edwards,
and
L.Regan
(2008).
Structure and function of KH domains.
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FEBS J,
275,
2712-2726.
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Z.Du,
S.Fenn,
R.Tjhen,
and
T.L.James
(2008).
Structure of a Construct of a Human Poly(C)-binding Protein Containing the First and Second KH Domains Reveals Insights into Its Regulatory Mechanisms.
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J Biol Chem,
283,
28757-28766.
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A.Barkan,
L.Klipcan,
O.Ostersetzer,
T.Kawamura,
Y.Asakura,
and
K.P.Watkins
(2007).
The CRM domain: an RNA binding module derived from an ancient ribosome-associated protein.
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RNA,
13,
55-64.
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B.M.Lunde,
C.Moore,
and
G.Varani
(2007).
RNA-binding proteins: modular design for efficient function.
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Nat Rev Mol Cell Biol,
8,
479-490.
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K.Januszyk,
P.W.Li,
V.Villareal,
D.Branciforte,
H.Wu,
Y.Xie,
J.Feigon,
J.A.Loo,
S.L.Martin,
and
R.T.Clubb
(2007).
Identification and solution structure of a highly conserved C-terminal domain within ORF1p required for retrotransposition of long interspersed nuclear element-1.
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J Biol Chem,
282,
24893-24904.
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PDB code:
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M.F.García-Mayoral,
D.Hollingworth,
L.Masino,
I.Díaz-Moreno,
G.Kelly,
R.Gherzi,
C.F.Chou,
C.Y.Chen,
and
A.Ramos
(2007).
The structure of the C-terminal KH domains of KSRP reveals a noncanonical motif important for mRNA degradation.
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Structure,
15,
485-498.
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PDB codes:
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M.Z.Jia,
J.Ohtsuka,
W.C.Lee,
K.Nagata,
and
M.Tanokura
(2007).
Crystal structure of Dim2p: a preribosomal RNA processing factor, from Pyrococcus horikoshii OT3 at 2.30 A.
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Proteins,
69,
428-432.
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PDB code:
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P.Banerjee,
S.Nayar,
S.Hebbar,
C.F.Fox,
M.C.Jacobs,
J.H.Park,
J.J.Fernandes,
and
T.C.Dockendorff
(2007).
Substitution of critical isoleucines in the KH domains of Drosophila fragile X protein results in partial loss-of-function phenotypes.
|
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Genetics,
175,
1241-1250.
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S.Fenn,
Z.Du,
J.K.Lee,
R.Tjhen,
R.M.Stroud,
and
T.L.James
(2007).
Crystal structure of the third KH domain of human poly(C)-binding protein-2 in complex with a C-rich strand of human telomeric DNA at 1.6 A resolution.
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Nucleic Acids Res,
35,
2651-2660.
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PDB code:
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S.Hare,
W.Fischer,
R.Williams,
L.Terradot,
R.Bayliss,
R.Haas,
and
G.Waksman
(2007).
Identification, structure and mode of action of a new regulator of the Helicobacter pylori HP0525 ATPase.
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EMBO J,
26,
4926-4934.
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PDB code:
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Z.Du,
J.K.Lee,
S.Fenn,
R.Tjhen,
R.M.Stroud,
and
T.L.James
(2007).
X-ray crystallographic and NMR studies of protein-protein and protein-nucleic acid interactions involving the KH domains from human poly(C)-binding protein-2.
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RNA,
13,
1043-1051.
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PDB codes:
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F.W.Scherrer,
and
M.Spingola
(2006).
A subset of Mer1p-dependent introns requires Bud13p for splicing activation and nuclear retention.
|
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RNA,
12,
1361-1372.
|
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J.Mercante,
K.Suzuki,
X.Cheng,
P.Babitzke,
and
T.Romeo
(2006).
Comprehensive alanine-scanning mutagenesis of Escherichia coli CsrA defines two subdomains of critical functional importance.
|
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J Biol Chem,
281,
31832-31842.
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J.Ule,
G.Stefani,
A.Mele,
M.Ruggiu,
X.Wang,
B.Taneri,
T.Gaasterland,
B.J.Blencowe,
and
R.B.Darnell
(2006).
An RNA map predicting Nova-dependent splicing regulation.
|
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Nature,
444,
580-586.
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N.H.Chmiel,
D.C.Rio,
and
J.A.Doudna
(2006).
Distinct contributions of KH domains to substrate binding affinity of Drosophila P-element somatic inhibitor protein.
|
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RNA,
12,
283-291.
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R.B.Darnell
(2006).
Developing global insight into RNA regulation.
|
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Cold Spring Harb Symp Quant Biol,
71,
321-327.
|
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S.D.Auweter,
F.C.Oberstrass,
and
F.H.Allain
(2006).
Sequence-specific binding of single-stranded RNA: is there a code for recognition?
|
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Nucleic Acids Res,
34,
4943-4959.
|
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T.P.Munro,
S.Kwon,
B.J.Schnapp,
and
D.St Johnston
(2006).
A repeated IMP-binding motif controls oskar mRNA translation and anchoring independently of Drosophila melanogaster IMP.
|
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J Cell Biol,
172,
577-588.
|
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Y.Hargous,
G.M.Hautbergue,
A.M.Tintaru,
L.Skrisovska,
A.P.Golovanov,
J.Stevenin,
L.Y.Lian,
S.A.Wilson,
and
F.H.Allain
(2006).
Molecular basis of RNA recognition and TAP binding by the SR proteins SRp20 and 9G8.
|
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EMBO J,
25,
5126-5137.
|
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PDB codes:
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B.Beuth,
S.Pennell,
K.B.Arnvig,
S.R.Martin,
and
I.A.Taylor
(2005).
Structure of a Mycobacterium tuberculosis NusA-RNA complex.
|
| |
EMBO J,
24,
3576-3587.
|
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PDB codes:
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B.K.Dredge,
G.Stefani,
C.C.Engelhard,
and
R.B.Darnell
(2005).
Nova autoregulation reveals dual functions in neuronal splicing.
|
| |
EMBO J,
24,
1608-1620.
|
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C.Bagni,
and
W.T.Greenough
(2005).
From mRNP trafficking to spine dysmorphogenesis: the roots of fragile X syndrome.
|
| |
Nat Rev Neurosci,
6,
376-387.
|
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I.Pozdnyakova,
and
L.Regan
(2005).
New insights into Fragile X syndrome. Relating genotype to phenotype at the molecular level.
|
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FEBS J,
272,
872-878.
|
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J.C.Darnell,
C.E.Fraser,
O.Mostovetsky,
G.Stefani,
T.A.Jones,
S.R.Eddy,
and
R.B.Darnell
(2005).
Kissing complex RNAs mediate interaction between the Fragile-X mental retardation protein KH2 domain and brain polyribosomes.
|
| |
Genes Dev,
19,
903-918.
|
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J.C.Darnell,
O.Mostovetsky,
and
R.B.Darnell
(2005).
FMRP RNA targets: identification and validation.
|
| |
Genes Brain Behav,
4,
341-349.
|
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J.Ule,
A.Ule,
J.Spencer,
A.Williams,
J.S.Hu,
M.Cline,
H.Wang,
T.Clark,
C.Fraser,
M.Ruggiu,
B.R.Zeeberg,
D.Kane,
J.N.Weinstein,
J.Blume,
and
R.B.Darnell
(2005).
Nova regulates brain-specific splicing to shape the synapse.
|
| |
Nat Genet,
37,
844-852.
|
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M.Sidiqi,
J.A.Wilce,
C.J.Porter,
A.Barker,
P.J.Leedman,
and
M.C.Wilce
(2005).
Formation of an alphaCP1-KH3 complex with UC-rich RNA.
|
| |
Eur Biophys J,
34,
423-429.
|
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|
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PDB codes:
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PDB code:
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Mol Cell Biol,
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Structure and function of the PWI motif: a novel nucleic acid-binding domain that facilitates pre-mRNA processing.
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Genes Dev,
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PDB code:
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D.L.Theobald,
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Nucleotide shuffling and ssDNA recognition in Oxytricha nova telomere end-binding protein complexes.
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EMBO J,
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PDB codes:
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H.Yang,
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CLIP identifies Nova-regulated RNA networks in the brain.
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Science,
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K.E.Lukong,
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Sam68, the KH domain-containing superSTAR.
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Biochim Biophys Acta,
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K.L.Farina,
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Two ZBP1 KH domains facilitate beta-actin mRNA localization, granule formation, and cytoskeletal attachment.
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J Cell Biol,
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The fragile X mental retardation protein FMRP binds elongation factor 1A mRNA and negatively regulates its translation in vivo.
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RNA,
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EMBO J,
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PDB code:
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G.J.Ostheimer,
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and
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Crystal structure of E. coli YhbY: a representative of a novel class of RNA binding proteins.
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Structure,
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PDB code:
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J.P.Staley
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Hanging on to the branch.
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Nat Struct Biol,
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An in vitro-selected RNA-binding site for the KH domain protein PSI acts as a splicing inhibitor element.
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RNA,
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CRS1 is a novel group II intron splicing factor that was derived from a domain of ancient origin.
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RNA,
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Mol Cell Biol,
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Identification of in vivo mRNA targets of GLD-1, a maxi-KH motif containing protein required for C. elegans germ cell development.
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The neural RNA-binding protein Musashi1 translationally regulates mammalian numb gene expression by interacting with its mRNA.
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Mol Cell Biol,
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Cloning and characterization of PIMT, a protein with a methyltransferase domain, which interacts with and enhances nuclear receptor coactivator PRIP function.
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PDB code:
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A.D.Frankel
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Fitting peptides into the RNA world.
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Curr Opin Struct Biol,
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Biochemistry,
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The tetranucleotide UCAY directs the specific recognition of RNA by the Nova K-homology 3 domain.
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Proc Natl Acad Sci U S A,
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A duplicated fold is the structural basis for polynucleotide phosphorylase catalytic activity, processivity, and regulation.
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PDB codes:
|
 |
|
|
|
|
|
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M.Spingola,
and
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A yeast intronic splicing enhancer and Nam8p are required for Mer1p-activated splicing.
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Mol Cell,
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P.B.Rupert,
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Structure,
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Genetic evidence for a Nova regulator of alternative splicing in the brain.
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Neuron,
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T.M.Soliman,
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Identification of an export control sequence and a requirement for the KH domains in ICP27 from herpes simplex virus type 1.
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J Virol,
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Cooperative assembly of an hnRNP complex induced by a tissue-specific homolog of polypyrimidine tract binding protein.
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Mol Cell Biol,
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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.
|
');
}
}
 |