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Science 26 May 1995:
Vol. 268. no. 5214, pp. 1173 - 1176
DOI: 10.1126/science.7761834
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Articles

Science, Vol 268, Issue 5214, 1173-1176
Copyright © 1995 by American Association for the Advancement of Science

articles

Distinct binding specificities and functions of higher eukaryotic polypyrimidine tract-binding proteins

R Singh, J Valcarcel, and MR Green

Howard Hughes Medical Institute, Program in Molecular Medicine, University of Massachusetts Medical Center, Worcester 01605, USA.

In higher eukaryotes, the polypyrimidine-tract (Py-tract) adjacent to the 3' splice site is recognized by several proteins, including the essential splicing factor U2AF65, the splicing regulator Sex-lethal (Sxl), and polypyrimidine tract-binding protein (PTB), whose function is unknown. Iterative in vitro genetic selection was used to show that these proteins have distinct sequence preferences. The uridine-rich degenerate sequences selected by U2AF65 are similar to those present in the diverse array of natural metazoan Py-tracts. In contrast, the Sxl-consensus is a highly specific sequence, which can help explain the ability of Sxl to regulate splicing of transformer pre-mRNA and autoregulate splicing of its own pre-mRNA. The PTB-consensus is not a typical Py-tract; it can be found in certain alternatively spliced pre-mRNAs that undergo negative regulation. Here it is shown that PTB can regulate alternative splicing by selectively repressing 3' splice sites that contain a PTB-binding site.


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RNA Binding Protein Sex-Lethal (Sxl) and Control of Drosophila Sex Determination and Dosage Compensation.
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   Abstract »    Full Text »    PDF »
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Antagonistic regulation of {alpha}-actinin alternative splicing by CELF proteins and polypyrimidine tract binding protein.
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Human cytomegalovirus UL37 immediate early target minigene RNAs are accurately spliced and polyadenylated.
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SRp30c Is a Repressor of 3' Splice Site Utilization.
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Splice Variants but not Mutations of DNA Polymerase {beta} Are Common in Bladder Cancer.
T. E. Thompson, P. K. Rogan, J. I. Risinger, and J. A. Taylor (2002)
Cancer Res. 62, 3251-3256
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HuD binds to three AU-rich sequences in the 3'-UTR of neuroserpin mRNA and promotes the accumulation of neuroserpin mRNA and protein.
A. Cuadrado, C. Navarro-Yubero, H. Furneaux, J. Kinter, P. Sonderegger, and A. Munoz (2002)
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R. P. Carstens, E. J. Wagner, and M. A. Garcia-Blanco (2000)
Mol. Cell. Biol. 20, 7388-7400
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Human Genomic Sequences That Inhibit Splicing.
W. G. Fairbrother and L. A. Chasin (2000)
Mol. Cell. Biol. 20, 6816-6825
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Multiple Splicing Defects in an Intronic False Exon.
H. Sun and L. A. Chasin (2000)
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Optimization of a Weak 3' Splice Site Counteracts the Function of a Bovine Papillomavirus Type 1 Exonic Splicing Suppressor In Vitro and In Vivo.
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Identification and Characterization of a Novel Serine-Arginine-Rich Splicing Regulatory Protein.
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Constitutive and regulated modes of splicing produce six major myotonic dystrophy protein kinase (DMPK) isoforms with distinct properties.
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Transient Expression of Cellular Polypyrimidine-Tract Binding Protein Stimulates Cap-Independent Translation Directed by Both Picornaviral and Flaviviral Internal Ribosome Entry Sites In Vivo.
R. Gosert, K. H. Chang, R. Rijnbrand, M. Yi, D. V. Sangar, and S. M. Lemon (2000)
Mol. Cell. Biol. 20, 1583-1595
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Identification of cis-Elements Regulating Exon 15 Splicing of the Amyloid Precursor Protein Pre-mRNA.
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   Abstract »    Full Text »    PDF »
Absence of interdomain contacts in the crystal structure of the RNA recognition motifs of Sex-lethal.
S. M. Crowder, R. Kanaar, D. C. Rio, and T. Alber (1999)
PNAS 96, 4892-4897
   Abstract »    Full Text »    PDF »
Polypyrimidine Tract Binding Protein Functions as a Repressor To Regulate Alternative Splicing of alpha -Actinin Mutally Exclusive Exons.
J. Southby, C. Gooding, and C. W. J. Smith (1999)
Mol. Cell. Biol. 19, 2699-2711
   Abstract »    Full Text »    PDF »
Polypyrimidine Tract-Binding Protein Positively Regulates Inclusion of an Alternative 3'-Terminal Exon.
H. Lou, D. M. Helfman, R. F. Gagel, and S. M. Berget (1999)
Mol. Cell. Biol. 19, 78-85
   Abstract »    Full Text »    PDF »
Multiple Distinct Splicing Enhancers in the Protein-Coding Sequences of a Constitutively Spliced Pre-mRNA.
T. D. Schaal and T. Maniatis (1999)
Mol. Cell. Biol. 19, 261-273
   Abstract »    Full Text »    PDF »
The Role of Evolutionarily Conserved Sequences in Alternative Splicing at the 3' End of Drosophila melanogaster Myosin Heavy Chain RNA.
D. Hodges, R. M. Cripps, M. E. O'Connor, and S. I. Bernstein (1999)
Genetics 151, 263-276
   Abstract »    Full Text »
Multiple Forms of the U2 Small Nuclear Ribonucleoprotein Auxiliary Factor U2AF Subunits Expressed in Higher Plants.
C. Domon, Z. J. Lorkovic, J. Valcarcel, and W. Filipowicz (1998)
J. Biol. Chem. 273, 34603-34610
   Abstract »    Full Text »    PDF »
{gamma}-Aminobutyric Acid Up-Regulates the Expression of a Novel Secretogranin-II Messenger Ribonucleic Acid in the Goldfish Pituitary.
M. Blazquez, P. T. Bosma, J. P. Chang, K. Docherty, and V. L. Trudeau (1998)
Endocrinology 139, 4870-4880
   Abstract »    Full Text »    PDF »
A pyrimidine-rich exonic splicing suppressor binds multiple RNA splicing factors and inhibits spliceosome assembly.
Z. M. Zheng, M. Huynen, and C. C. Baker (1998)
PNAS 95, 14088-14093
   Abstract »    Full Text »    PDF »
Controlling Gene Expression in Living Cells Through Small Molecule-RNA Interactions.
G. Werstuck and M. R. Green (1998)
Science 282, 296-298
   Abstract »    Full Text »
The Perinucleolar Compartment and Transcription.
S. Huang, T. J. Deerinck, M. H. Ellisman, and D. L. Spector (1998)
J. Cell Biol. 143, 35-47
   Abstract »    Full Text »    PDF »


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