Distinct binding specificities and functions of higher eukaryotic polypyrimidine tract-binding proteins.
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.
Singh
R
R
Howard Hughes Medical Institute, Program in Molecular Medicine, University of Massachusetts Medical Center, Worcester 01605, USA.
Valcárcel
J
J
Green
M R
MR
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D016384:Consensus Sequence; D018076:DNA, Complementary; D004330:Drosophila; D029721:Drosophila Proteins; D005260:Female; D006801:Humans; D007301:Insect Hormones / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D038941:Polypyrimidine Tract-Binding Protein; D012326:RNA Splicing; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism*; D000072668:Splicing Factor U2AF
D018076:DNA, Complementary; D029721:Drosophila Proteins; D007301:Insect Hormones; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D000072668:Splicing Factor U2AF; C067777:Sxl protein, Drosophila; C000607494:U2AF2 protein, human; D038941:Polypyrimidine Tract-Binding Protein