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* Residue conservation analysis
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PDB id:
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RNA binding protein
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Title:
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Solution structure of the third RNA recognition motif (rrm) of u2af65 in complex with an n-terminal sf1 peptide
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Structure:
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Splicing factor u2af 65 kda subunit. Chain: a. Fragment: c-terminal rrm domain. Synonym: u2 auxiliary factor 65 kda subunit, u2 snrnp auxiliary factor large subunit, hu2af(65). Engineered: yes. Splicing factor sf1. Chain: b. Fragment: n-terminal peptide.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: the peptide was chemically synthesized and derived from the n-terminus of sf1. The sequence of the peptide is naturally found in homo sapiens (human).
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NMR struc:
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10 models
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Authors:
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P.Selenko,G.Gregorovic,R.Sprangers,G.Stier,Z.Rhani,A.Kramer,M.Sattler
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Key ref:
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P.Selenko
et al.
(2003).
Structural basis for the molecular recognition between human splicing factors U2AF65 and SF1/mBBP.
Mol Cell,
11,
965-976.
PubMed id:
DOI:
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Date:
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24-Feb-03
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Release date:
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06-May-03
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PROCHECK
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Headers
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References
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Enzyme class:
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Chains A, B:
E.C.?
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DOI no:
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Mol Cell
11:965-976
(2003)
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PubMed id:
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Structural basis for the molecular recognition between human splicing factors U2AF65 and SF1/mBBP.
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P.Selenko,
G.Gregorovic,
R.Sprangers,
G.Stier,
Z.Rhani,
A.Krämer,
M.Sattler.
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ABSTRACT
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The essential splicing factors SF1 and U2AF play an important role in the
recognition of the pre-mRNA 3' splice site during early spliceosome assembly.
The structure of the C-terminal RRM (RRM3) of human U2AF(65) complexed to an
N-terminal peptide of SF1 reveals an extended negatively charged helix A and an
additional helix C. Helix C shields the potential RNA binding surface. SF1 binds
to the opposite, helical face of RRM3. It inserts a conserved tryptophan into a
hydrophobic pocket between helices A and B in a way that strikingly resembles
part of the molecular interface in the U2AF heterodimer. This molecular
recognition establishes a paradigm for protein binding by a subfamily of
noncanonical RRMs.
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Selected figure(s)
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Figure 4.
Figure 4. Tryptophan Recognition by the U2AF^35 RRM and
U2AF^65-RRM3(A) Ribbon representation of the U2AF^35 RRM in
complex with the proline-rich region in the N terminus of
U2AF^65 (Kielkopf et al., 2001). Side chains involved in the
molecular interface are shown. Trp134, which is not conserved in
U2AF^65-RRM3, is labeled magenta.(B) Ribbon representation of
the U2AF^65-RRM3/SF1 complex. Side chains involved in tryptophan
coordination are shown.(C) Sequence alignment of noncanonical
RRMs with an extended and negatively charged helix A.
Conserved residues that mediate recognition of SF1 Trp22 and
U2AF^65 Trp92 by U2AF^65-RRM3 and the U2AF^35 RRM, respectively,
are shown in white on black. Trp134 in the U2AF^35 RRM is
colored magenta.(D) Domain organization of proteins that contain
noncanonical RRMs. The domain annotations are according to SMART
(Schultz et al., 1998). “R/S” is an arginine-serine-rich
region, “STY Kc” is a phoshokinase domain, and “Zn” are
zinc binding domains.
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Figure 6.
Figure 6. Structure and Topology of Complex E during
Spliceosome AssemblyFor a description, see the text. An
additional interaction between the R/S domain of U2AF^65 and the
BPS (Valcárcel et al., 1996) is not shown.
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The above figures are
reprinted
by permission from Cell Press:
Mol Cell
(2003,
11,
965-976)
copyright 2003.
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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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A.G.Murachelli,
J.Ebert,
C.Basquin,
H.Le Hir,
and
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(2012).
The structure of the ASAP core complex reveals the existence of a Pinin-containing PSAP complex.
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Nat Struct Mol Biol,
19,
378-386.
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PDB codes:
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M.Corioni,
N.Antih,
G.Tanackovic,
M.Zavolan,
and
A.Krämer
(2011).
Analysis of in situ pre-mRNA targets of human splicing factor SF1 reveals a function in alternative splicing.
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Nucleic Acids Res,
39,
1868-1879.
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Q.Yang,
M.Coseno,
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and
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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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C.D.Cukier,
D.Hollingworth,
S.R.Martin,
G.Kelly,
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Molecular basis of FIR-mediated c-myc transcriptional control.
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Nat Struct Mol Biol,
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J.Chang,
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and
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(2010).
Mutational analyses of trimethylguanosine synthase (Tgs1) and Mud2: proteins implicated in pre-mRNA splicing.
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RNA,
16,
1018-1031.
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L.Elantak,
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and
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The indispensable N-terminal half of eIF3j/HCR1 cooperates with its structurally conserved binding partner eIF3b/PRT1-RRM and with eIF1A in stringent AUG selection.
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J Mol Biol,
396,
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A.Eulalio,
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and
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(2009).
The RRM domain in GW182 proteins contributes to miRNA-mediated gene silencing.
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Nucleic Acids Res,
37,
2974-2983.
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PDB code:
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C.de Chiara,
R.P.Menon,
M.Strom,
T.J.Gibson,
and
A.Pastore
(2009).
Phosphorylation of s776 and 14-3-3 binding modulate ataxin-1 interaction with splicing factors.
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PLoS One,
4,
e8372.
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J.H.Lee,
E.S.Rangarajan,
S.D.Yogesha,
and
T.Izard
(2009).
Raver1 interactions with vinculin and RNA suggest a feed-forward pathway in directing mRNA to focal adhesions.
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Structure,
17,
833-842.
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PDB codes:
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L.Corsini,
M.Hothorn,
G.Stier,
V.Rybin,
K.Scheffzek,
T.J.Gibson,
and
M.Sattler
(2009).
Dimerization and Protein Binding Specificity of the U2AF Homology Motif of the Splicing Factor Puf60.
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J Biol Chem,
284,
630-639.
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PDB code:
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L.Ma,
and
H.R.Horvitz
(2009).
Mutations in the Caenorhabditis elegans U2AF large subunit UAF-1 alter the choice of a 3' splice site in vivo.
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PLoS Genet,
5,
e1000708.
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M.A.Brooks,
A.Dziembowski,
S.Quevillon-Cheruel,
V.Henriot,
C.Faux,
H.van Tilbeurgh,
and
B.Séraphin
(2009).
Structure of the yeast Pml1 splicing factor and its integration into the RES complex.
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Nucleic Acids Res,
37,
129-143.
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PDB code:
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A.Cléry,
M.Blatter,
and
F.H.Allain
(2008).
RNA recognition motifs: boring? Not quite.
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Curr Opin Struct Biol,
18,
290-298.
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C.R.Mandel,
Y.Bai,
and
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(2008).
Protein factors in pre-mRNA 3'-end processing.
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Cell Mol Life Sci,
65,
1099-1122.
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G.Toba,
and
K.White
(2008).
The third RNA recognition motif of Drosophila ELAV protein has a role in multimerization.
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Nucleic Acids Res,
36,
1390-1399.
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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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J.L.Jenkins,
H.Shen,
M.R.Green,
and
C.L.Kielkopf
(2008).
Solution Conformation and Thermodynamic Characteristics of RNA Binding by the Splicing Factor U2AF65.
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J Biol Chem,
283,
33641-33649.
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J.M.Izquierdo
(2008).
Fas splicing regulation during early apoptosis is linked to caspase-mediated cleavage of U2AF65.
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Mol Biol Cell,
19,
3299-3307.
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J.Rino,
J.M.Desterro,
T.R.Pacheco,
T.W.Gadella,
and
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(2008).
Splicing factors SF1 and U2AF associate in extraspliceosomal complexes.
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Mol Cell Biol,
28,
3045-3057.
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J.Sperling,
M.Azubel,
and
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Structure and function of the Pre-mRNA splicing machine.
|
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Structure,
16,
1605-1615.
|
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|
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K.Kuwasako,
N.Dohmae,
M.Inoue,
M.Shirouzu,
S.Taguchi,
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B.Séraphin,
Y.Muto,
and
S.Yokoyama
(2008).
Complex assembly mechanism and an RNA-binding mode of the human p14-SF3b155 spliceosomal protein complex identified by NMR solution structure and functional analyses.
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Proteins,
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1617-1636.
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M.Teplova,
and
D.J.Patel
(2008).
Structural insights into RNA recognition by the alternative-splicing regulator muscleblind-like MBNL1.
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Nat Struct Mol Biol,
15,
1343-1351.
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PDB codes:
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P.Tompa,
and
M.Fuxreiter
(2008).
Fuzzy complexes: polymorphism and structural disorder in protein-protein interactions.
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Trends Biochem Sci,
33,
2-8.
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S.Trowitzsch,
G.Weber,
R.Lührmann,
and
M.C.Wahl
(2008).
An unusual RNA recognition motif acts as a scaffold for multiple proteins in the pre-mRNA retention and splicing complex.
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J Biol Chem,
283,
32317-32327.
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V.Manceau,
C.L.Kielkopf,
A.Sobel,
and
A.Maucuer
(2008).
Different requirements of the kinase and UHM domains of KIS for its nuclear localization and binding to splicing factors.
|
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J Mol Biol,
381,
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B.M.Lunde,
C.Moore,
and
G.Varani
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RNA-binding proteins: modular design for efficient function.
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8,
479-490.
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C.A.Galloway,
C.MacElrevey,
M.P.Sowden,
J.E.Wedekind,
and
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(2007).
Functional characterization of APOBEC-1 complementation factor phosphorylation sites.
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Biochim Biophys Acta,
1773,
408-418.
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L.Corsini,
S.Bonnal,
S.Bonna,
J.Basquin,
M.Hothorn,
K.Scheffzek,
J.Valcárcel,
and
M.Sattler
(2007).
U2AF-homology motif interactions are required for alternative splicing regulation by SPF45.
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Nat Struct Mol Biol,
14,
620-629.
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PDB codes:
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L.ElAntak,
A.G.Tzakos,
N.Locker,
and
P.J.Lukavsky
(2007).
Structure of eIF3b RNA recognition motif and its interaction with eIF3j: structural insights into the recruitment of eIF3b to the 40 S ribosomal subunit.
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J Biol Chem,
282,
8165-8174.
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PDB code:
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S.D.Shaw,
S.Chakrabarti,
G.Ghosh,
and
A.R.Krainer
(2007).
Deletion of the N-terminus of SF2/ASF permits RS-domain-independent pre-mRNA splicing.
|
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PLoS ONE,
2,
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A.P.Rideau,
C.Gooding,
P.J.Simpson,
T.P.Monie,
M.Lorenz,
S.Hüttelmaier,
R.H.Singer,
S.Matthews,
S.Curry,
and
C.W.Smith
(2006).
A peptide motif in Raver1 mediates splicing repression by interaction with the PTB RRM2 domain.
|
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Nat Struct Mol Biol,
13,
839-848.
|
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I.A.Turner,
C.M.Norman,
M.J.Churcher,
and
A.J.Newman
(2006).
Dissection of Prp8 protein defines multiple interactions with crucial RNA sequences in the catalytic core of the spliceosome.
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RNA,
12,
375-386.
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K.R.Thickman,
M.C.Swenson,
J.M.Kabogo,
Z.Gryczynski,
and
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(2006).
Multiple U2AF65 binding sites within SF3b155: thermodynamic and spectroscopic characterization of protein-protein interactions among pre-mRNA splicing factors.
|
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J Mol Biol,
356,
664-683.
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M.J.Schellenberg,
R.A.Edwards,
D.B.Ritchie,
O.A.Kent,
M.M.Golas,
H.Stark,
R.Lührmann,
J.N.Glover,
and
A.M.MacMillan
(2006).
Crystal structure of a core spliceosomal protein interface.
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Proc Natl Acad Sci U S A,
103,
1266-1271.
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PDB codes:
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R.Spadaccini,
U.Reidt,
O.Dybkov,
C.Will,
R.Frank,
G.Stier,
L.Corsini,
M.C.Wahl,
R.Lührmann,
and
M.Sattler
(2006).
Biochemical and NMR analyses of an SF3b155-p14-U2AF-RNA interaction network involved in branch point definition during pre-mRNA splicing.
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RNA,
12,
410-425.
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S.Caputo,
J.Couprie,
I.Duband-Goulet,
E.Kondé,
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S.Braud,
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H.J.Worman,
and
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(2006).
The carboxyl-terminal nucleoplasmic region of MAN1 exhibits a DNA binding winged helix domain.
|
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J Biol Chem,
281,
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PDB code:
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V.Manceau,
M.Swenson,
J.P.Le Caer,
A.Sobel,
C.L.Kielkopf,
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Major phosphorylation of SF1 on adjacent Ser-Pro motifs enhances interaction with U2AF65.
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273,
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The Shwachman-Bodian-Diamond syndrome protein family is involved in RNA metabolism.
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PDB codes:
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C.D.Mackereth,
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and
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(2005).
Extending the size of protein-RNA complexes studied by nuclear magnetic resonance spectroscopy.
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Analysis of mutant phenotypes and splicing defects demonstrates functional collaboration between the large and small subunits of the essential splicing factor U2AF in vivo.
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Mol Biol Cell,
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C.Maris,
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272,
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Human splicing factor SF3a, but not SF1, is essential for pre-mRNA splicing in vivo.
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R.Singh,
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Polypyrimidine tract binding protein blocks the 5' splice site-dependent assembly of U2AF and the prespliceosomal E complex.
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FEBS J,
272,
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The splicing factor U2AF small subunit is functionally conserved between fission yeast and humans.
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| |
Mol Cell Biol,
24,
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S.Lücke,
and
M.R.Green
(2004).
U2AF homology motifs: protein recognition in the RRM world.
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| |
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18,
1513-1526.
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| |
Plant J,
38,
875-886.
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S.Guth,
J.Valcarcel,
and
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(2004).
The conserved RNA recognition motif 3 of U2 snRNA auxiliary factor (U2AF 65) is essential in vivo but dispensable for activity in vitro.
|
| |
RNA,
10,
240-253.
|
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J.Kadlec,
E.Izaurralde,
and
S.Cusack
(2004).
The structural basis for the interaction between nonsense-mediated mRNA decay factors UPF2 and UPF3.
|
| |
Nat Struct Mol Biol,
11,
330-337.
|
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PDB code:
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M.Blanchette,
E.Labourier,
R.E.Green,
S.E.Brenner,
and
D.C.Rio
(2004).
Genome-wide analysis reveals an unexpected function for the Drosophila splicing factor U2AF50 in the nuclear export of intronless mRNAs.
|
| |
Mol Cell,
14,
775-786.
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S.Dettwiler,
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(2004).
Distinct sequence motifs within the 68-kDa subunit of cleavage factor Im mediate RNA binding, protein-protein interactions, and subcellular localization.
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J Biol Chem,
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G.Varani,
and
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Splicing factor 1 in the pocket.
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Structure,
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O.A.Kent,
A.Reayi,
L.Foong,
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(2003).
Structuring of the 3' splice site by U2AF65.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
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only a partial list as not all journals are covered by
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so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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